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<th valign="BASELINE" nowrap="nowrap" align="RIGHT">Asunto:
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<td> NEW YEAR LECTURE<br>
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<th valign="BASELINE" nowrap="nowrap" align="RIGHT">Fecha: </th>
<td>Thu, 06 Jan 2022 15:09:26 +0100</td>
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<th valign="BASELINE" nowrap="nowrap" align="RIGHT">De: </th>
<td>Youri Timsit <a class="moz-txt-link-rfc2396E" href="mailto:youri.timsit@mio.osupytheas.fr"><youri.timsit@mio.osupytheas.fr></a></td>
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<th valign="BASELINE" nowrap="nowrap" align="RIGHT">Para: </th>
<td>Pedro C. Marijuán <a class="moz-txt-link-rfc2396E" href="mailto:pedroc.marijuan@gmail.com"><pedroc.marijuan@gmail.com></a></td>
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line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB">Happy
New Year to all! <br>
</span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><br>
<span style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB"><o:p></o:p></span></p>
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style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB">First
of all I would like to warmly
thank Pedro Marijuán for having offered me to contribute to
this New Year lecture.
It is a great pleasure to exchange ideas in a context where
“informational
choreography” </span><!--[if supportFields]><span lang=EN-GB style='font-size:
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style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"R12X5N9H","properties":{"formattedCitation":"\\super
1\\nosupersub{}","plainCitation":"1","noteIndex":0},"citationItems":[{"id":580,"uris":["http://zotero.org/users/local/yyYzumuD/items/JHKLLW8V"],"uri":["http://zotero.org/users/local/yyYzumuD/items/JHKLLW8V"],"itemData":{"id":580,"type":"article-journal","abstract":"Understanding
the nature of life has always been a fundamental objective of human knowledge.
It is no wonder that biology, as the science of life, together with physics,
has traditionally been the discipline that has generated the deepest
philosophical and social repercussions. In our time, the major achievements in
bioinformatics, systems biology, and \"omic\" fields (genomics,
proteomics, metabolomics, etc.) have not only spurred a new biotechnological
and biomedical 'postindustrial revolution', but they have also disclosed an
intriguing molecular panorama of biological organization that invites us to
reinterpret central themes of philosophy in the light of the new knowledge.
Essential tenets of phenomenology may take an intriguing new turn when
contemplated from these new biological perspectives: Does the living cell
instantiate a unique biomolecular way of being in the world? How is life
self-produced in continuous communication with the surrounding world? How can
the incessant flows of mass, energy and information inherent of embodiment be
coherently harnessed across billions of cellular individuals? In this paper,
based on the latest developments in cellular signaling, we will discuss the
dynamic intertwining between self-production and communication that
characterizes life at the prokaryotic, eukaryotic, organismic, and social
levels of organization. An in-depth analysis of the particular transcriptional
responses of a bacterium (Escherichia coli K-12 strain), taking as a model
system, will follow. It is the creation, transmission and reception of signals
which, in all instances, provides guidance and orientation to the inner
self-production activities of the living agent and connects it with the world.
Transitions to new levels of organization are marked by the emergence of new
forms of communication, embedded in the correspondingly augmented life-cycles
of the more complex entities. As will be argued here, the ascending complexity
of life is always information-based and recapitulates level after level, a
successful \"informational formula\" for being in the world. The
phenomenological basis for the naturalization of cognition has moved from the
biological to a new scientific arena: informational. The philosophical notion
of being-in-the-world (Dasein; Heidegger) is shown to be completely compatible
with the latest advances in biology and information
science.","container-title":"Progress in Biophysics and
Molecular Biology","DOI":"10.1016/j.pbiomolbio.2015.07.002","ISSN":"1873-1732","issue":"3","journalAbbreviation":"Prog
Biophys Mol Biol","language":"eng","note":"PMID:
26169771","page":"469-480","source":"PubMed","title":"How
the living is in the world: An inquiry into the informational choreographies of
life","title-short":"How the living is in the
world","volume":"119","author":[{"family":"Marijuán","given":"Pedro
C."},{"family":"Navarro","given":"Jorge"},{"family":"Moral","given":"Raquel","non-dropping-particle":"del"}],"issued":{"date-parts":[["2015",12]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">1</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB"> allows for imaginary encounters between
Isadora Duncan and José Ortega y Gasset, to explore new ways
of thinking about “what is life”. The topic of
this new year lecture is “molecular brains”, a theme that
has recently been
developed on the basis of recent work on the ribosome </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"MwCOEipo","properties":{"formattedCitation":"\\super
2\\nosupersub{}","plainCitation":"2","noteIndex":0},"citationItems":[{"id":6553,"uris":["http://zotero.org/users/local/yyYzumuD/items/N2GE2EJL"],"uri":["http://zotero.org/users/local/yyYzumuD/items/N2GE2EJL"],"itemData":{"id":6553,"type":"article-journal","abstract":"How
can single cells without nervous systems perform complex behaviours such as
habituation, associative learning and decision making, which are considered the
hallmark of animals with a brain? Are there molecular systems that underlie
cognitive properties equivalent to those of the brain? This review follows the
development of the idea of molecular brains from Darwin’s “root brain
hypothesis”, through bacterial chemotaxis, to the recent discovery of
neuron-like r-protein networks in the ribosome. By combining a structural
biology view with a Bayesian brain approach, this review explores the
evolutionary labyrinth of information processing systems across scales.
Ribosomal protein networks open a window into what were probably the earliest signalling
systems to emerge before the radiation of the three kingdoms. While ribosomal
networks are characterised by long-lasting interactions between their protein
nodes, cell signalling networks are essentially based on transient
interactions. As a corollary, while signals propagated in persistent networks
may be ephemeral, networks whose interactions are transient constrain signals
diffusing into the cytoplasm to be durable in time, such as post-translational
modifications of proteins or second messenger synthesis. The duration and
nature of the signals, in turn, implies different mechanisms for the
integration of multiple signals and decision making. Evolution then reinvented
networks with persistent interactions with the development of nervous systems in
metazoans. Ribosomal protein networks and simple nervous systems display
architectural and functional analogies whose comparison could suggest scale
invariance in information processing. At the molecular level, the significant
complexification of eukaryotic ribosomal protein networks is associated with a
burst in the acquisition of new conserved aromatic amino acids. Knowing that
aromatic residues play a critical role in allosteric receptors and channels,
this observation suggests a general role of </span><span style='font-size:10.0pt;
line-height:150%;font-family:"ＭＳ 明朝";mso-ascii-font-family:Times;mso-fareast-font-family:
"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Times;
mso-ansi-language:EN-GB'>π</span><span lang=EN-GB style='font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB'> systems and their
interactions with charged amino acids in multiple signal integration and
information processing. We think that these findings may provide the molecular
basis for designing future computers with organic
processors.","container-title":"International Journal of
Molecular
Sciences","DOI":"10.3390/ijms222111868","issue":"21","language":"en","note":"number:
21\npublisher: Multidisciplinary Digital Publishing Institute","page":"11868","source":"www.mdpi.com","title":"Towards
the Idea of Molecular Brains","volume":"22","author":[{"family":"Timsit","given":"Youri"},{"family":"Grégoire","given":"Sergeant-Perthuis"}],"issued":{"date-parts":[["2021",1]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">2</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">, D. Bray's seminal paper
published in 1995 </span><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"RLKRhEfb","properties":{"formattedCitation":"\\super
3\\nosupersub{}","plainCitation":"3","noteIndex":0},"citationItems":[{"id":509,"uris":["http://zotero.org/users/local/yyYzumuD/items/9FBS98J7"],"uri":["http://zotero.org/users/local/yyYzumuD/items/9FBS98J7"],"itemData":{"id":509,"type":"article-journal","abstract":"Many
proteins in living cells appear to have as their primary function the transfer
and processing of information, rather than the chemical transformation of
metabolic intermediates or the building of cellular structures. Such proteins
are functionally linked through allosteric or other mechanisms into biochemical
'circuits' that perform a variety of simple computational tasks including
amplification, integration and information
storage.","container-title":"Nature","DOI":"10.1038/376307a0","ISSN":"0028-0836","issue":"6538","journalAbbreviation":"Nature","language":"eng","note":"PMID:
7630396","page":"307-312","source":"PubMed","title":"Protein
molecules as computational elements in living
cells","volume":"376","author":[{"family":"Bray","given":"D."}],"issued":{"date-parts":[["1995",7,27]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">3</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB"> and the recent papers about consciousness in
non-neural organisms </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"FmZRck7W","properties":{"formattedCitation":"\\super
4\\nosupersub{}","plainCitation":"4","noteIndex":0},"citationItems":[{"id":5042,"uris":["http://zotero.org/users/local/yyYzumuD/items/35MIR4KX"],"uri":["http://zotero.org/users/local/yyYzumuD/items/35MIR4KX"],"itemData":{"id":5042,"type":"article-journal","abstract":"Cells
emerged at the very beginning of life on Earth and, in fact, are coterminous
with life. They are enclosed within an excitable plasma membrane, which defines
the outside and inside domains via their specific biophysical properties.
Unicellular organisms, such as diverse protists and algae, still live a
cellular life. However, fungi, plants, and animals evolved a multicellular
existence. Recently, we have developed the cellular basis of consciousness
(CBC) model, which proposes that all biological awareness, sentience and
consciousness are grounded in general cell biology. Here we discuss the
biomolecular structures and processes that allow for and maintain this cellular
consciousness from an evolutionary
perspective.","container-title":"International Journal of
Molecular Sciences","DOI":"10.3390/ijms22052545","issue":"5","language":"en","note":"number:
5\npublisher: Multidisciplinary Digital Publishing
Institute","page":"2545","source":"www.mdpi.com","title":"Biomolecular
Basis of Cellular Consciousness via Subcellular
Nanobrains","volume":"22","author":[{"family":"Baluška","given":"František"},{"family":"Miller","given":"William
B."},{"family":"Reber","given":"Arthur
S."}],"issued":{"date-parts":[["2021",1]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">4</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB"><o:p></o:p></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB"> </span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB">Are
“molecular brains” a “vision of
the mind” or a real property of matter and universe, born
from the first forms
of life? And as a corollary, did LUCA have a brain
(molecular) and was he “intelligent”?
And to go even further, is having systems capable of
developing complex
behaviours and cognitive faculties a fundamental property of
living beings
across scales? I hope that future works will shed light on
these questions, but
in the meantime, I present here briefly, the elements that
led to the conclusion
that systems equivalent of “neural networks” on a molecular
scale could exist
in the ribosome and that these systems most probably existed
before the
radiation of the three kingdoms. <o:p></o:p></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB"> </span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB">The
ribosome is indeed considered as
window towards the earliest forms of life that predate the
three kingdoms. While
in astrophysics looking far away gives the opportunity to
glimpse the fossil
radiation of the universe, looking into the heart of the
ribosome may tell us
of what the first forms of life might have looked like. The
ribosome evolved by
accretion around a core that predates the radiation of the
three kingdoms and were
probably present in LUCA </span><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"vf2mgH7T","properties":{"formattedCitation":"\\super
5\\uc0\\u8211{}9\\nosupersub{}","plainCitation":"5–9","noteIndex":0},"citationItems":[{"id":33,"uris":["http://zotero.org/users/local/yyYzumuD/items/2DJWXCW4"],"uri":["http://zotero.org/users/local/yyYzumuD/items/2DJWXCW4"],"itemData":{"id":33,"type":"article-journal","abstract":"Structural
analysis, supported by biochemical, mutagenesis and computational evidence,
indicates that the peptidyltransferase centre of the contemporary ribosome is a
universal symmetrical pocket composed solely of rRNA. This pocket seems to be a
relic of the proto-ribosome, an ancient ribozyme, which was a dimeric RNA
assembly formed from self-folded RNA chains of identical, similar or different
sequences. This could have occurred spontaneously by gene duplication or gene
fusion. This pocket-like entity was capable of autonomously catalysing various
reactions, including peptide bond formation and non-coded or semi-coded amino
acid polymerization. Efforts toward the structural definition of the early
entity capable of genetic decoding involve the crystallization of the small
ribosomal subunit of a bacterial organism harbouring a single functional rRNA
operon.","container-title":"Biochemical Society
Transactions","DOI":"10.1042/BST0380422","ISSN":"1470-8752","issue":"2","journalAbbreviation":"Biochem.
Soc.
Trans.","language":"eng","note":"PMID:
20298195","page":"422-427","source":"PubMed","title":"Ancient
machinery embedded in the contemporary ribosome","volume":"38","author":[{"family":"Belousoff","given":"Matthew
J."},{"family":"Davidovich","given":"Chen"},{"family":"Zimmerman","given":"Ella"},{"family":"Caspi","given":"Yaron"},{"family":"Wekselman","given":"Itai"},{"family":"Rozenszajn","given":"Lin"},{"family":"Shapira","given":"Tal"},{"family":"Sade-Falk","given":"Ofir"},{"family":"Taha","given":"Leena"},{"family":"Bashan","given":"Anat"},{"family":"Weiss","given":"Manfred
S."},{"family":"Yonath","given":"Ada"}],"issued":{"date-parts":[["2010",4]]}}},{"id":16,"uris":["http://zotero.org/users/local/yyYzumuD/items/FSD74KSM"],"uri":["http://zotero.org/users/local/yyYzumuD/items/FSD74KSM"],"itemData":{"id":16,"type":"article-journal","abstract":"The
modern ribosome was largely formed at the time of the last common ancestor,
LUCA. Hence its earliest origins likely lie in the RNA world. Central to its
development were RNAs that spawned the modern tRNAs and a symmetrical region
deep within the large ribosomal RNA, (rRNA), where the peptidyl transferase
reaction occurs. To understand pre-LUCA developments, it is argued that events
that are coupled in time are especially useful if one can infer a likely order
in which they occurred. Using such timing events, the relative age of various
proteins and individual regions within the large rRNA are inferred. An
examination of the properties of modern ribosomes strongly suggests that the
initial peptides made by the primitive ribosomes were likely enriched for
l-amino acids, but did not completely exclude d-amino acids. This has
implications for the nature of peptides made by the first ribosomes. From the
perspective of ribosome origins, the immediate question regarding coding is
when did it arise rather than how did the assignments evolve. The modern
ribosome is very dynamic with tRNAs moving in and out and the mRNA moving
relative to the ribosome. These movements may have become possible as a result
of the addition of a template to hold the tRNAs. That template would
subsequently become the mRNA, thereby allowing the evolution of the code and
making an RNA genome useful. Finally, a highly speculative timeline of major events
in ribosome history is presented and possible future directions
discussed.","container-title":"Cold Spring Harbor
Perspectives in
Biology","DOI":"10.1101/cshperspect.a003483","ISSN":"1943-0264","issue":"9","journalAbbreviation":"Cold
Spring Harb Perspect
Biol","language":"eng","note":"PMID:
20534711\nPMCID:
PMC2926754","page":"a003483","source":"PubMed","title":"Origin
and evolution of the ribosome","volume":"2","author":[{"family":"Fox","given":"George
E."}],"issued":{"date-parts":[["2010",9]]}}},{"id":273,"uris":["http://zotero.org/users/local/yyYzumuD/items/CXMCK7FG"],"uri":["http://zotero.org/users/local/yyYzumuD/items/CXMCK7FG"],"itemData":{"id":273,"type":"article-journal","abstract":"Ribosomes
are among the largest and most dynamic molecular motors. The structure and
dynamics of translation initiation and elongation are reviewed. Three ribosome
motions have been identified for initiation and translocation. A swivel motion
between the head/beak and the body of the 30S subunit was observed. A tilting
dynamic of the head/beak versus the body of the 30S subunit was detected using
simulations. A reversible ratcheting motion was seen between the 30S and the
50S subunits that slide relative to one another. The 30S</span><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Palatino;
mso-bidi-font-family:Palatino;mso-ansi-language:EN-GB'>⁻</span><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'>50S intersubunit contacts regulate translocation. IF2,
EF-Tu, and EF-G are homologous G-protein GTPases that cycle on and off the same
site on the ribosome. The ribosome, aminoacyl-tRNA synthetase (aaRS) enzymes,
transfer ribonucleic acid (tRNA), and messenger ribonucleic acid (mRNA) form
the core of information processing in cells and are coevolved. Surprisingly,
class I and class II aaRS enzymes, with distinct and incompatible folds, are
homologs. Divergence of class I and class II aaRS enzymes and coevolution of
the genetic code are described by analysis of ancient archaeal
species.","container-title":"International Journal of
Molecular
Sciences","DOI":"10.3390/ijms20010040","ISSN":"1422-0067","issue":"1","journalAbbreviation":"Int
J Mol
Sci","language":"eng","note":"PMID:
30583477\nPMCID: PMC6337491","source":"PubMed","title":"Ribosome
Structure, Function, and Early
Evolution","volume":"20","author":[{"family":"Opron","given":"Kristopher"},{"family":"Burton","given":"Zachary
F."}],"issued":{"date-parts":[["2018",12,21]]}}},{"id":7,"uris":["http://zotero.org/users/local/yyYzumuD/items/HTF29ET4"],"uri":["http://zotero.org/users/local/yyYzumuD/items/HTF29ET4"],"itemData":{"id":7,"type":"article-journal","abstract":"Ribosomes
are universally conserved enzymes that carry out protein biosynthesis. Bacterial
and eukaryotic ribosomes, which share an evolutionarily conserved core, are
thought to have evolved from a common ancestor by addition of proteins and RNA
that bestow different functionalities to ribosomes from different domains of
life. Recently, structures of the eukaryotic ribosome, determined by X-ray
crystallography, have allowed us to compare these structures to previously
determined structures of bacterial ribosomes. Here we describe selected
bacteria- or eukaryote-specific structural features of the ribosome and discuss
the functional implications of some of
them.","container-title":"Nature Structural & Molecular
Biology","DOI":"10.1038/nsmb.2313","ISSN":"1545-9985","issue":"6","journalAbbreviation":"Nat.
Struct. Mol. Biol.","language":"eng","note":"PMID:
22664983","page":"560-567","source":"PubMed","title":"One
core, two shells: bacterial and eukaryotic
ribosomes","title-short":"One core, two shells","volume":"19","author":[{"family":"Melnikov","given":"Sergey"},{"family":"Ben-Shem","given":"Adam"},{"family":"Garreau
de
Loubresse","given":"Nicolas"},{"family":"Jenner","given":"Lasse"},{"family":"Yusupova","given":"Gulnara"},{"family":"Yusupov","given":"Marat"}],"issued":{"date-parts":[["2012",6,5]]}}},{"id":37,"uris":["http://zotero.org/users/local/yyYzumuD/items/3CP9JLC6"],"uri":["http://zotero.org/users/local/yyYzumuD/items/3CP9JLC6"],"itemData":{"id":37,"type":"article-journal","abstract":"A
comprehensive investigation of ribosomal genes in complete genomes from 66
different species allows us to address the distribution of r-proteins between
and within the three primary domains. Thirty-four r-protein families are
represented in all domains but 33 families are specific to Archaea and Eucarya,
providing evidence for specialisation at an early stage of evolution between
the bacterial lineage and the lineage leading to Archaea and Eukaryotes. With
only one specific r-protein, the archaeal ribosome appears to be a small-scale
model of the eukaryotic one in terms of protein composition. However, the mechanism
of evolution of the protein component of the ribosome appears dramatically
different in Archaea. In Bacteria and Eucarya, a restricted number of ribosomal
genes can be lost with a bias toward losses in intracellular pathogens. In
Archaea, losses implicate 15% of the ribosomal genes revealing an unexpected
plasticity of the translation apparatus and the pattern of gene losses
indicates a progressive elimination of ribosomal genes in the course of
archaeal evolution. This first documented case of reductive evolution at the
domain scale provides a new framework for discussing the shape of the universal
tree of life and the selective forces directing the evolution of
prokaryotes.","container-title":"Nucleic Acids
Research","DOI":"10.1093/nar/gkf693","ISSN":"1362-4962","issue":"24","journalAbbreviation":"Nucleic
Acids
Res.","language":"eng","note":"PMID:
12490706\nPMCID: PMC140077","page":"5382-5390","source":"PubMed","title":"Comparative
analysis of ribosomal proteins in complete genomes: an example of reductive
evolution at the domain scale","title-short":"Comparative
analysis of ribosomal proteins in complete
genomes","volume":"30","author":[{"family":"Lecompte","given":"Odile"},{"family":"Ripp","given":"Raymond"},{"family":"Thierry","given":"Jean-Claude"},{"family":"Moras","given":"Dino"},{"family":"Poch","given":"Olivier"}],"issued":{"date-parts":[["2002",12,15]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">5–9</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">. The ribosomes are
thus considered as a relic of
ancient translation systems that co-evolved with the genetic
code have evolved
by the accretion of rRNA and ribosomal (r)-proteins around a
universal core </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"hN5B7IQh","properties":{"formattedCitation":"\\super
8,10\\uc0\\u8211{}14\\nosupersub{}","plainCitation":"8,10–14","noteIndex":0},"citationItems":[{"id":7,"uris":["http://zotero.org/users/local/yyYzumuD/items/HTF29ET4"],"uri":["http://zotero.org/users/local/yyYzumuD/items/HTF29ET4"],"itemData":{"id":7,"type":"article-journal","abstract":"Ribosomes
are universally conserved enzymes that carry out protein biosynthesis.
Bacterial and eukaryotic ribosomes, which share an evolutionarily conserved
core, are thought to have evolved from a common ancestor by addition of
proteins and RNA that bestow different functionalities to ribosomes from
different domains of life. Recently, structures of the eukaryotic ribosome,
determined by X-ray crystallography, have allowed us to compare these
structures to previously determined structures of bacterial ribosomes. Here we
describe selected bacteria- or eukaryote-specific structural features of the
ribosome and discuss the functional implications of some of
them.","container-title":"Nature Structural & Molecular
Biology","DOI":"10.1038/nsmb.2313","ISSN":"1545-9985","issue":"6","journalAbbreviation":"Nat.
Struct. Mol.
Biol.","language":"eng","note":"PMID:
22664983","page":"560-567","source":"PubMed","title":"One
core, two shells: bacterial and eukaryotic ribosomes","title-short":"One
core, two
shells","volume":"19","author":[{"family":"Melnikov","given":"Sergey"},{"family":"Ben-Shem","given":"Adam"},{"family":"Garreau
de
Loubresse","given":"Nicolas"},{"family":"Jenner","given":"Lasse"},{"family":"Yusupova","given":"Gulnara"},{"family":"Yusupov","given":"Marat"}],"issued":{"date-parts":[["2012",6,5]]}}},{"id":19,"uris":["http://zotero.org/users/local/yyYzumuD/items/7NZWUL8J"],"uri":["http://zotero.org/users/local/yyYzumuD/items/7NZWUL8J"],"itemData":{"id":19,"type":"article-journal","abstract":"We
present a molecular-level model for the origin and evolution of the translation
system, using a 3D comparative method. In this model, the ribosome evolved by
accretion, recursively adding expansion segments, iteratively growing, subsuming,
and freezing the rRNA. Functions of expansion segments in the ancestral
ribosome are assigned by correspondence with their functions in the extant
ribosome. The model explains the evolution of the large ribosomal subunit, the
small ribosomal subunit, tRNA, and mRNA. Prokaryotic ribosomes evolved in six
phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit
association, correlated evolution, decoding, energy-driven translocation, and
surface proteinization. Two additional phases exclusive to eukaryotes led to
tentacle-like rRNA expansions. In this model, ribosomal proteinization was a
driving force for the broad adoption of proteins in other biological processes.
The exit tunnel was clearly a central theme of all phases of ribosomal
evolution and was continuously extended and rigidified. In the primitive
noncoding ribosome, proto-mRNA and the small ribosomal subunit acted as
cofactors, positioning the activated ends of tRNAs within the peptidyl
transferase center. This association linked the evolution of the large and
small ribosomal subunits, proto-mRNA, and
tRNA.","container-title":"Proceedings of the National
Academy of Sciences of the United States of
America","DOI":"10.1073/pnas.1509761112","ISSN":"1091-6490","issue":"50","journalAbbreviation":"Proc.
Natl. Acad. Sci.
U.S.A.","language":"eng","note":"PMID:
26621738\nPMCID:
PMC4687566","page":"15396-15401","source":"PubMed","title":"History
of the ribosome and the origin of
translation","volume":"112","author":[{"family":"Petrov","given":"Anton
S."},{"family":"Gulen","given":"Burak"},{"family":"Norris","given":"Ashlyn
M."},{"family":"Kovacs","given":"Nicholas
A."},{"family":"Bernier","given":"Chad
R."},{"family":"Lanier","given":"Kathryn
A."},{"family":"Fox","given":"George
E."},{"family":"Harvey","given":"Stephen
C."},{"family":"Wartell","given":"Roger
M."},{"family":"Hud","given":"Nicholas
V."},{"family":"Williams","given":"Loren
Dean"}],"issued":{"date-parts":[["2015",12,15]]}}},{"id":301,"uris":["http://zotero.org/users/local/yyYzumuD/items/XBLLK6NA"],"uri":["http://zotero.org/users/local/yyYzumuD/items/XBLLK6NA"],"itemData":{"id":301,"type":"article-journal","abstract":"The
principles of mRNA decoding are conserved among all extant life forms. We
present an integrative view of all the interaction networks between mRNA, tRNA
and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation
of the anticodon hairpin, the presence of modified nucleotides, the occurrence
of non-Watson-Crick pairs in the codon-anticodon helix and the interactions
with bases of rRNA at the A-site decoding site. We derive a more
information-rich, alternative representation of the genetic code, that is
circular with an unsymmetrical distribution of codons leading to a clear
segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon
boxes. All tRNA sequence variations can be visualized, within an internal
structural and energy framework, for each organism, and each anticodon of the
sense codons. The multiplicity and complexity of nucleotide modifications at
positions 34 and 37 of the anticodon loop segregate meaningfully, and correlate
well with the necessity to stabilize AU-rich codon-anticodon pairs and to avoid
miscoding in split codon boxes. The evolution and expansion of the genetic code
is viewed as being originally based on GC content with progressive introduction
of A/U together with tRNA modifications. The representation we present should
help the engineering of the genetic code to include non-natural amino acids.","container-title":"Nucleic
Acids
Research","DOI":"10.1093/nar/gkw608","ISSN":"1362-4962","issue":"17","journalAbbreviation":"Nucleic
Acids Res.","language":"eng","note":"PMID:
27448410\nPMCID:
PMC5041475","page":"8020-8040","source":"PubMed","title":"An
integrated, structure- and energy-based view of the genetic
code","volume":"44","author":[{"family":"Grosjean","given":"Henri"},{"family":"Westhof","given":"Eric"}],"issued":{"date-parts":[["2016"]],"season":"30"}}},{"id":257,"uris":["http://zotero.org/users/local/yyYzumuD/items/J4EFL3X3"],"uri":["http://zotero.org/users/local/yyYzumuD/items/J4EFL3X3"],"itemData":{"id":257,"type":"article-journal","abstract":"Many
steps in the evolution of cellular life are still mysterious. We suggest that
the ribosome may represent one important missing link between compositional (or
metabolism-first), RNA-world (or genes-first) and cellular (last universal
common ancestor) approaches to the evolution of cells. We present evidence that
the entire set of transfer RNAs for all twenty amino acids are encoded in both
the 16S and 23S rRNAs of Escherichia coli K12; that nucleotide sequences that
could encode key fragments of ribosomal proteins, polymerases, ligases,
synthetases, and phosphatases are to be found in each of the six possible
reading frames of the 16S and 23S rRNAs; and that every sequence of bases in
rRNA has information encoding more than one of these functions in addition to
acting as a structural component of the ribosome. Ribosomal RNA, in short, is
not just a structural scaffold for proteins, but the vestigial remnant of a
primordial genome that may have encoded a self-organizing, self-replicating,
auto-catalytic intermediary between macromolecules and cellular
life.","container-title":"Journal of Theoretical
Biology","DOI":"10.1016/j.jtbi.2014.11.025","ISSN":"1095-8541","journalAbbreviation":"J.
Theor.
Biol.","language":"eng","note":"PMID:
25500179","page":"130-158","source":"PubMed","title":"The
ribosome as a missing link in the evolution of
life","volume":"367","author":[{"family":"Root-Bernstein","given":"Meredith"},{"family":"Root-Bernstein","given":"Robert"}],"issued":{"date-parts":[["2015",2,21]]}}},{"id":"qobbXeQd/yql4pH46","uris":["http://zotero.org/users/local/yyYzumuD/items/72RAD8PX"],"uri":["http://zotero.org/users/local/yyYzumuD/items/72RAD8PX"],"itemData":{"id":4184,"type":"article-journal","abstract":"We
have proposed that the ribosome may represent a missing link between prebiotic
chemistries and the first cells. One of the predictions that follows from this
hypothesis, which we test here, is that ribosomal RNA (rRNA) must have encoded
the proteins necessary for ribosomal function. In other words, the rRNA also
functioned pre-biotically as mRNA. Since these ribosome-binding proteins
(rb-proteins) must bind to the rRNA, but the rRNA also functioned as mRNA, it
follows that rb-proteins should bind to their own mRNA as well. This hypothesis
can be contrasted to a \"null\" hypothesis in which rb-proteins
evolved independently of the rRNA sequences and therefore there should be no
necessary similarity between the rRNA to which rb-proteins bind and the mRNA
that encodes the rb-protein. Five types of evidence reported here support the
plausibility of the hypothesis that the mRNA encoding rb-proteins evolved from rRNA:
(1) the ubiquity of rb-protein binding to their own mRNAs and autogenous
control of their own translation; (2) the higher-than-expected incidence of
Arginine-rich modules associated with RNA binding that occurs in rRNA-encoded
proteins; (3) the fact that rRNA-binding regions of rb-proteins are homologous
to their mRNA binding regions; (4) the higher than expected incidence of
rb-protein sequences encoded in rRNA that are of a high degree of homology to
their mRNA as compared with a random selection of other proteins; and (5) rRNA
in modern prokaryotes and eukaryotes encodes functional proteins. None of these
results can be explained by the null hypothesis that assumes independent
evolution of rRNA and the mRNAs encoding ribosomal proteins. Also noteworthy is
that very few proteins bind their own mRNAs that are not associated with
ribosome function. Further tests of the hypothesis are suggested: (1)
experimental testing of whether rRNA-encoded proteins bind to rRNA at their
coding sites; (2) whether tRNA synthetases, which are also known to bind to
their own mRNAs, are encoded by the tRNA sequences themselves; (3) and the
prediction that archaeal and prokaryotic (DNA-based) genomes were built around
rRNA \"genes\" so that rRNA-related sequences will be found to make
up an unexpectedly high proportion of these
genomes.","container-title":"Journal of Theoretical
Biology","DOI":"10.1016/j.jtbi.2016.02.030","ISSN":"1095-8541","journalAbbreviation":"J
Theor
Biol","language":"eng","note":"PMID:
26953650","page":"115-127","source":"PubMed","title":"The
ribosome as a missing link in prebiotic evolution II: Ribosomes encode
ribosomal proteins that bind to common regions of their own mRNAs and
rRNAs","title-short":"The ribosome as a missing link in
prebiotic evolution II","volume":"397","author":[{"family":"Root-Bernstein","given":"Robert"},{"family":"Root-Bernstein","given":"Meredith"}],"issued":{"date-parts":[["2016",5,21]]}}},{"id":4180,"uris":["http://zotero.org/users/local/yyYzumuD/items/3BUDR52Z"],"uri":["http://zotero.org/users/local/yyYzumuD/items/3BUDR52Z"],"itemData":{"id":4180,"type":"article-journal","abstract":"We
propose that ribosomal RNA (rRNA) formed the basis of the first cellular
genomes, and provide evidence from a review of relevant literature and proteonomic
tests. We have proposed previously that the ribosome may represent the vestige
of the first self-replicating entity in which rRNAs also functioned as genes
that were transcribed into functional messenger RNAs (mRNAs) encoding ribosomal
proteins. rRNAs also encoded polymerases to replicate itself and a full
complement of the transfer RNAs (tRNAs) required to translate its genes. We
explore here a further prediction of our \"ribosome-first\" theory:
the ribosomal genome provided the basis for the first cellular genomes. Modern
genomes should therefore contain an unexpectedly large percentage of tRNA- and
rRNA-like modules derived from both sense and antisense reading frames, and
these should encode non-ribosomal proteins, as well as ribosomal ones with key
cell functions. Ribosomal proteins should also have been co-opted by cellular
evolution to play extra-ribosomal functions. We review existing literature
supporting these predictions. We provide additional, new data demonstrating
that rRNA-like sequences occur at significantly higher frequencies than
predicted on the basis of mRNA duplications or randomized RNA sequences. These
data support our \"ribosome-first\" theory of cellular
evolution.","container-title":"International Journal of
Molecular Sciences","DOI":"10.3390/ijms20010140","ISSN":"1422-0067","issue":"1","journalAbbreviation":"Int
J Mol
Sci","language":"eng","note":"PMID:
30609737\nPMCID:
PMC6337102","source":"PubMed","title":"The
Ribosome as a Missing Link in Prebiotic Evolution III: Over-Representation of
tRNA- and rRNA-Like Sequences and Plieofunctionality of Ribosome-Related
Molecules Argues for the Evolution of Primitive Genomes from Ribosomal RNA
Modules","title-short":"The Ribosome as a Missing Link in
Prebiotic Evolution III","volume":"20","author":[{"family":"Root-Bernstein","given":"Robert"},{"family":"Root-Bernstein","given":"Meredith"}],"issued":{"date-parts":[["2019",1,2]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">8,10–14</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">. They then followed
distinct evolutionary pathways to
form the bacterial, archaeal and eukaryotic ribosomes whose
overall structures
are well conserved within kingdoms </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"s2Uk7cKA","properties":{"formattedCitation":"\\super
15\\uc0\\u8211{}18\\nosupersub{}","plainCitation":"15–18","noteIndex":0},"citationItems":[{"id":56,"uris":["http://zotero.org/users/local/yyYzumuD/items/9H63AUTZ"],"uri":["http://zotero.org/users/local/yyYzumuD/items/9H63AUTZ"],"itemData":{"id":56,"type":"article-journal","abstract":"The
sequential addition of amino acids to a growing polypeptide chain is carried
out by the ribosome in a complicated multistep process called the elongation
cycle. It involves accurate selection of each aminoacyl tRNA as dictated by the
mRNA codon, catalysis of peptide bond formation, and movement of the tRNAs and
mRNA through the ribosome. The process requires the GTPase factors elongation
factor Tu (EF-Tu) and EF-G. Not surprisingly, large conformational changes in both
the ribosome and its tRNA substrates occur throughout protein elongation. Major
advances in our understanding of the elongation cycle have been made in the
past few years as a result of high-resolution crystal structures that capture
various states of the process, as well as biochemical and computational
studies.","container-title":"Annual Review of
Biochemistry","DOI":"10.1146/annurev-biochem-113009-092313","ISSN":"1545-4509","journalAbbreviation":"Annu.
Rev.
Biochem.","language":"eng","note":"PMID:
23746255","page":"203-236","source":"PubMed","title":"Structural
basis of the translational elongation
cycle","volume":"82","author":[{"family":"Voorhees","given":"Rebecca
M."},{"family":"Ramakrishnan","given":"V."}],"issued":{"date-parts":[["2013"]]}}},{"id":387,"uris":["http://zotero.org/users/local/yyYzumuD/items/X5W2H5YI"],"uri":["http://zotero.org/users/local/yyYzumuD/items/X5W2H5YI"],"itemData":{"id":387,"type":"article-journal","abstract":"The
large ribosomal subunit catalyzes peptide bond formation and binds initiation,
termination, and elongation factors. We have determined the crystal structure
of the large ribosomal subunit from Haloarcula marismortui at 2.4 angstrom
resolution, and it includes 2833 of the subunit's 3045 nucleotides and 27 of
its 31 proteins. The domains of its RNAs all have irregular shapes and fit
together in the ribosome like the pieces of a three-dimensional jigsaw puzzle
to form a large, monolithic structure. Proteins are abundant everywhere on its
surface except in the active site where peptide bond formation occurs and where
it contacts the small subunit. Most of the proteins stabilize the structure by
interacting with several RNA domains, often using idiosyncratically folded
extensions that reach into the subunit's interior.","container-title":"Science
(New York,
N.Y.)","DOI":"10.1126/science.289.5481.905","ISSN":"0036-8075","issue":"5481","journalAbbreviation":"Science","language":"eng","note":"PMID:
10937989","page":"905-920","source":"PubMed","title":"The
complete atomic structure of the large ribosomal subunit at 2.4 A
resolution","volume":"289","author":[{"family":"Ban","given":"N."},{"family":"Nissen","given":"P."},{"family":"Hansen","given":"J."},{"family":"Moore","given":"P.
B."},{"family":"Steitz","given":"T.
A."}],"issued":{"date-parts":[["2000",8,11]]}}},{"id":114,"uris":["http://zotero.org/users/local/yyYzumuD/items/3UKKUK6K"],"uri":["http://zotero.org/users/local/yyYzumuD/items/3UKKUK6K"],"itemData":{"id":114,"type":"article-journal","abstract":"Ribosomes
translate genetic information encoded by messenger RNA into proteins. Many
aspects of translation and its regulation are specific to eukaryotes, whose
ribosomes are much larger and intricate than their bacterial counterparts. We
report the crystal structure of the 80S ribosome from the yeast Saccharomyces
cerevisiae--including nearly all ribosomal RNA bases and protein side chains as
well as an additional protein, Stm1--at a resolution of 3.0 angstroms. This
atomic model reveals the architecture of eukaryote-specific elements and their
interaction with the universally conserved core, and describes all
eukaryote-specific bridges between the two ribosomal subunits. It forms the
structural framework for the design and analysis of experiments that explore
the eukaryotic translation apparatus and the evolutionary forces that shaped
it.","container-title":"Science (New York,
N.Y.)","DOI":"10.1126/science.1212642","ISSN":"1095-9203","issue":"6062","journalAbbreviation":"Science","language":"eng","note":"PMID:
22096102","page":"1524-1529","source":"PubMed","title":"The
structure of the eukaryotic ribosome at 3.0 Å
resolution","volume":"334","author":[{"family":"Ben-Shem","given":"Adam"},{"family":"Garreau
de
Loubresse","given":"Nicolas"},{"family":"Melnikov","given":"Sergey"},{"family":"Jenner","given":"Lasse"},{"family":"Yusupova","given":"Gulnara"},{"family":"Yusupov","given":"Marat"}],"issued":{"date-parts":[["2011",12,16]]}}},{"id":13,"uris":["http://zotero.org/users/local/yyYzumuD/items/PWZYYPWM"],"uri":["http://zotero.org/users/local/yyYzumuD/items/PWZYYPWM"],"itemData":{"id":13,"type":"article-journal","abstract":"Structures
of the bacterial ribosome have provided a framework for understanding universal
mechanisms of protein synthesis. However, the eukaryotic ribosome is much
larger than it is in bacteria, and its activity is fundamentally different in
many key ways. Recent cryo-electron microscopy reconstructions and X-ray
crystal structures of eukaryotic ribosomes and ribosomal subunits now provide
an unprecedented opportunity to explore mechanisms of eukaryotic translation
and its regulation in atomic detail. This review describes the X-ray crystal
structures of the Tetrahymena thermophila 40S and 60S subunits and the
Saccharomyces cerevisiae 80S ribosome, as well as cryo-electron microscopy
reconstructions of translating yeast and plant 80S ribosomes. Mechanistic
questions about translation in eukaryotes that will require additional
structural insights to be resolved are also
presented.","container-title":"Cold Spring Harbor
Perspectives in
Biology","DOI":"10.1101/cshperspect.a011536","ISSN":"1943-0264","issue":"5","journalAbbreviation":"Cold
Spring Harb Perspect Biol","language":"eng","note":"PMID:
22550233\nPMCID:
PMC3331703","source":"PubMed","title":"The
structure and function of the eukaryotic
ribosome","volume":"4","author":[{"family":"Wilson","given":"Daniel
N."},{"family":"Doudna
Cate","given":"Jamie H."}],"issued":{"date-parts":[["2012",5,1]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">15–18</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">. The complexity of
ribosome assemblies, structures,
efficiencies and translation fidelity concomitantly
increased in course of the
evolution. <o:p></o:p></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB"> </span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB">The
molecular brain’s story started
with an attempt to understand the surprising electrostatic
properties of the
bL20 ribosomal protein (r-protein), a protein essential for
the assembly of the
large subunit of the bacterial ribosome </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"CREpNtRk","properties":{"formattedCitation":"\\super
19\\nosupersub{}","plainCitation":"19","noteIndex":0},"citationItems":[{"id":141,"uris":["http://zotero.org/users/local/yyYzumuD/items/4YBV82KG"],"uri":["http://zotero.org/users/local/yyYzumuD/items/4YBV82KG"],"itemData":{"id":141,"type":"article-journal","abstract":"The
assignment of specific ribosomal functions to individual ribosomal proteins is
difficult due to the enormous cooperativity of the ribosome; however, important
roles for distinct ribosomal proteins are becoming evident. Although rRNA has a
major role in certain aspects of ribosomal function, such as decoding and
peptidyl-transferase activity, ribosomal proteins are nevertheless essential
for the assembly and optimal functioning of the ribosome. This is particularly
true in the context of interactions at the entrance pore for mRNA, for the
translation-factor binding site and at the tunnel exit, where both chaperones
and complexes associated with protein transport through membranes
bind.","container-title":"Critical Reviews in Biochemistry
and Molecular
Biology","DOI":"10.1080/10409230500256523","ISSN":"1040-9238","issue":"5","journalAbbreviation":"Crit.
Rev. Biochem. Mol. Biol.","language":"eng","note":"PMID:
16257826","page":"243-267","source":"PubMed","title":"Ribosomal
proteins in the spotlight","volume":"40","author":[{"family":"Wilson","given":"Daniel
N."},{"family":"Nierhaus","given":"Knud
H."}],"issued":{"date-parts":[["2005",10]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">19</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">. This r-protein had a kind of subversive and
unique behaviour in
deciding to crystallize in both a folded and an unfolded
form within the same
crystal </span><!--[if supportFields]><span lang=EN-GB style='font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"9sK9QmiD","properties":{"formattedCitation":"\\super
20\\nosupersub{}","plainCitation":"20","noteIndex":0},"citationItems":[{"id":197,"uris":["http://zotero.org/users/local/yyYzumuD/items/TWGSKRDW"],"uri":["http://zotero.org/users/local/yyYzumuD/items/TWGSKRDW"],"itemData":{"id":197,"type":"article-journal","abstract":"The
recent finding of intrinsically unstructured proteins defies the classical
structure-function paradigm. However, owing to their flexibility, intrinsically
unstructured proteins generally escape detailed structural investigations.
Consequently little is known about the extent of conformational disorder and
its role in biological functions. Here, we present the X-ray structure of the
unbound ribosomal protein L20, the long basic amino-terminal extension of which
has been previously interpreted as fully disordered in the absence of RNA. This
study provides the first detailed picture of two protein folding states trapped
together in a crystal and indicates that unfolding occurs in discrete regions
of the whole protein, corresponding mainly to RNA-binding residues. The
electrostatic destabilization of the long alpha-helix and a structural
communication between the two L20 domains are reminiscent of those observed in
calmodulin. The detailed comparison of the two conformations observed in the
crystal provides new insights into the role of unfolded extensions in ribosomal
assembly.","container-title":"EMBO
reports","DOI":"10.1038/sj.embor.7400803","ISSN":"1469-221X","issue":"10","journalAbbreviation":"EMBO
Rep.","language":"eng","note":"PMID:
16977336\nPMCID: PMC1618378","page":"1013-1018","source":"PubMed","title":"Coexistence
of two protein folding states in the crystal structure of ribosomal protein
L20","volume":"7","author":[{"family":"Timsit","given":"Youri"},{"family":"Allemand","given":"Fréderic"},{"family":"Chiaruttini","given":"Claude"},{"family":"Springer","given":"Mathias"}],"issued":{"date-parts":[["2006",10]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">20</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">. In trying to better understand its
properties, we compared it to the
other r-proteins located in the first high-resolution
ribosome structures that
had just been published </span><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"av3yY4V7","properties":{"formattedCitation":"\\super
21\\nosupersub{}","plainCitation":"21","noteIndex":0},"citationItems":[{"id":6556,"uris":["http://zotero.org/users/local/yyYzumuD/items/BKJFGK6W"],"uri":["http://zotero.org/users/local/yyYzumuD/items/BKJFGK6W"],"itemData":{"id":6556,"type":"article-journal","abstract":"The
crystal structure of the bacterial 70S ribosome refined to 2.8 angstrom
resolution reveals atomic details of its interactions with messenger RNA (mRNA)
and transfer RNA (tRNA). A metal ion stabilizes a kink in the mRNA that
demarcates the ...","archive_location":"world","container-title":"Science","DOI":"10.1126/science.1131127","language":"EN","note":"publisher:
American Association for the Advancement of
Science","source":"www-science-org.insb.bib.cnrs.fr","title":"Structure
of the 70S Ribosome Complexed with mRNA and tRNA","URL":"http://www.science.org/doi/abs/10.1126/science.1131127","author":[{"family":"Selmer","given":"Maria"},{"family":"Dunham","given":"Christine
M."},{"family":"Frank V.
Murphy","given":"I.
V."},{"family":"Weixlbaumer","given":"Albert"},{"family":"Petry","given":"Sabine"},{"family":"Kelley","given":"Ann
C."},{"family":"Weir","given":"John
R."},{"family":"Ramakrishnan","given":"V."}],"accessed":{"date-parts":[["2022",1,5]]},"issued":{"date-parts":[["2006",9,29]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">21</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">... and that's when something strange was
noticed: we realized that uL13
and uL3, two r-proteins of the large subunit, were touching
each other by a
tenuous interaction between their two extensions, long
filaments that weave
between the phosphate groups of the rRNA. At that time,
these famous r-protein
extensions were a real enigma. It was thought that they
could play a role in
ribosome assembly by neutralising RNA phosphates with their
positively charged
amino acids </span><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"bHUKc2Gr","properties":{"formattedCitation":"\\super
22\\nosupersub{}","plainCitation":"22","noteIndex":0},"citationItems":[{"id":194,"uris":["http://zotero.org/users/local/yyYzumuD/items/52NRUKEY"],"uri":["http://zotero.org/users/local/yyYzumuD/items/52NRUKEY"],"itemData":{"id":194,"type":"article-journal","abstract":"Although
during the past decade research has shown the functional importance of disorder
in proteins, many of the structural and dynamics properties of intrinsically
unstructured proteins (IUPs) remain to be elucidated. This review is focused on
the role of the extensions of the ribosomal proteins in the early steps of the
assembly of the eubacterial 50 S subunit. The recent crystallographic
structures of the ribosomal particles have revealed the picture of a complex
assembly pathway that condenses the rRNA and the ribosomal proteins into active
ribosomes. However, little is know about the molecular mechanisms of this
process. It is thought that the long basic r-protein extensions that penetrate
deeply into the subunit cores play a key role through disorder-order
transitions and/or co-folding mechanisms. A current view is that such
structural transitions may facilitate the proper rRNA folding. In this paper,
the structures of the proteins L3, L4, L13, L20, L22 and L24 that have been
experimentally found to be essential for the first steps of ribosome assembly
have been compared. On the basis of their structural and dynamics properties,
three categories of extensions have been identified. Each of them seems to play
a distinct function. Among them, only the coil-helix transition that occurs in
a phylogenetically conserved cluster of basic residues of the L20 extension
appears to be strictly required for the large subunit assembly in eubacteria.
The role of alpha helix-coil transitions in 23 S RNA folding is discussed in
the light of the calcium binding protein calmodulin that shares many structural
and dynamics properties with L20.","container-title":"International
Journal of Molecular
Sciences","DOI":"10.3390/ijms10030817","ISSN":"1422-0067","issue":"3","journalAbbreviation":"Int
J Mol Sci","language":"eng","note":"PMID:
19399222\nPMCID:
PMC2672003","page":"817-834","source":"PubMed","title":"The
role of disordered ribosomal protein extensions in the early steps of
eubacterial 50 S ribosomal subunit
assembly","volume":"10","author":[{"family":"Timsit","given":"Youri"},{"family":"Acosta","given":"Zahir"},{"family":"Allemand","given":"Frédéric"},{"family":"Chiaruttini","given":"Claude"},{"family":"Springer","given":"Mathias"}],"issued":{"date-parts":[["2009",3]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">22</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">. But gradually it became apparent that all
extensions of r-proteins
systematically wove a gigantic network based on tiny
interactions between them.
In general, when proteins interact with partners, they form
large interfaces
(> 2000 Å<sup>2</sup>) sufficient to stabilise their
interactions. In this
case, the vast majority of the interfaces did not exceed 200
Å<sup>2</sup>,
which is all the more surprising given that they were
extremely conserved
phylogenetically </span><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"0EnqyIBs","properties":{"formattedCitation":"\\super
23\\nosupersub{}","plainCitation":"23","noteIndex":0},"citationItems":[{"id":85,"uris":["http://zotero.org/users/local/yyYzumuD/items/6E5XWXNM"],"uri":["http://zotero.org/users/local/yyYzumuD/items/6E5XWXNM"],"itemData":{"id":85,"type":"article-journal","abstract":"From
brain to the World Wide Web, information-processing networks share common scale
invariant properties. Here, we reveal the existence of neural-like networks at
a molecular scale within the ribosome. We show that with their extensions, ribosomal
proteins form complex assortative interaction networks through which they
communicate through tiny interfaces. The analysis of the crystal structures of
50S eubacterial particles reveals that most of these interfaces involve key
phylogenetically conserved residues. The systematic observation of interactions
between basic and aromatic amino acids at the interfaces and along the
extension provides new structural insights that may contribute to decipher the
molecular mechanisms of signal transmission within or between the ribosomal
proteins. Similar to neurons interacting through \"molecular
synapses\", ribosomal proteins form a network that suggest an analogy with
a simple molecular brain in which the \"sensory-proteins\" innervate
the functional ribosomal sites, while the \"inter-proteins\"
interconnect them into circuits suitable to process the information flow that
circulates during protein synthesis. It is likely that these circuits have
evolved to coordinate both the complex macromolecular motions and the binding
of the multiple factors during translation. This opens new perspectives on
nanoscale information transfer and
processing.","container-title":"Scientific
Reports","DOI":"10.1038/srep26485","ISSN":"2045-2322","journalAbbreviation":"Sci
Rep","language":"eng","note":"PMID:
27225526\nPMCID:
PMC4881015","page":"26485","source":"PubMed","title":"Neuron-Like
Networks Between Ribosomal Proteins Within the Ribosome","volume":"6","author":[{"family":"Poirot","given":"Olivier"},{"family":"Timsit","given":"Youri"}],"issued":{"date-parts":[["2016"]],"season":"26"}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">23</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">. <o:p></o:p></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:10.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB"> </span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><span
style="font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">Strikingly, it was
found that the r-protein network also interacted with or
“innervate” the
ribosome functional centres such as tRNA sites, the Peptidyl
Transfer Centre (PTC),
and the peptide tunnel </span><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"m3XdFN0J","properties":{"formattedCitation":"\\super
23,24\\nosupersub{}","plainCitation":"23,24","noteIndex":0},"citationItems":[{"id":251,"uris":["http://zotero.org/users/local/yyYzumuD/items/6D9H4RRP"],"uri":["http://zotero.org/users/local/yyYzumuD/items/6D9H4RRP"],"itemData":{"id":251,"type":"article-journal","abstract":"In
the past few decades, studies on translation have converged towards the
metaphor of a \"ribosome nanomachine\"; they also revealed intriguing
ribosome properties challenging this view. Many studies have shown that to
perform an accurate protein synthesis in a fluctuating cellular environment, ribosomes
sense, transfer information and even make decisions. This complex
\"behaviour\" that goes far beyond the skills of a simple mechanical
machine has suggested that the ribosomal protein networks could play a role
equivalent to nervous circuits at a molecular scale to enable information
transfer and processing during translation. We analyse here the significance of
this analogy and establish a preliminary link between two fields: ribosome
structure-function studies and the analysis of information processing systems.
This cross-disciplinary analysis opens new perspectives about the mechanisms of
information transfer and processing in ribosomes and may provide new conceptual
frameworks for the understanding of the behaviours of unicellular organisms.","container-title":"International
Journal of Molecular
Sciences","DOI":"10.3390/ijms20122911","ISSN":"1422-0067","issue":"12","journalAbbreviation":"Int
J Mol Sci","language":"eng","note":"PMID:
31207893\nPMCID:
PMC6627100","source":"PubMed","title":"Nervous-Like
Circuits in the Ribosome Facts, Hypotheses and
Perspectives","volume":"20","author":[{"family":"Timsit","given":"Youri"},{"family":"Bennequin","given":"Daniel"}],"issued":{"date-parts":[["2019",6,14]]}}},{"id":85,"uris":["http://zotero.org/users/local/yyYzumuD/items/6E5XWXNM"],"uri":["http://zotero.org/users/local/yyYzumuD/items/6E5XWXNM"],"itemData":{"id":85,"type":"article-journal","abstract":"From
brain to the World Wide Web, information-processing networks share common scale
invariant properties. Here, we reveal the existence of neural-like networks at
a molecular scale within the ribosome. We show that with their extensions,
ribosomal proteins form complex assortative interaction networks through which
they communicate through tiny interfaces. The analysis of the crystal
structures of 50S eubacterial particles reveals that most of these interfaces
involve key phylogenetically conserved residues. The systematic observation of
interactions between basic and aromatic amino acids at the interfaces and along
the extension provides new structural insights that may contribute to decipher
the molecular mechanisms of signal transmission within or between the ribosomal
proteins. Similar to neurons interacting through \"molecular
synapses\", ribosomal proteins form a network that suggest an analogy with
a simple molecular brain in which the \"sensory-proteins\" innervate
the functional ribosomal sites, while the \"inter-proteins\"
interconnect them into circuits suitable to process the information flow that
circulates during protein synthesis. It is likely that these circuits have
evolved to coordinate both the complex macromolecular motions and the binding
of the multiple factors during translation. This opens new perspectives on
nanoscale information transfer and
processing.","container-title":"Scientific
Reports","DOI":"10.1038/srep26485","ISSN":"2045-2322","journalAbbreviation":"Sci
Rep","language":"eng","note":"PMID:
27225526\nPMCID:
PMC4881015","page":"26485","source":"PubMed","title":"Neuron-Like
Networks Between Ribosomal Proteins Within the
Ribosome","volume":"6","author":[{"family":"Poirot","given":"Olivier"},{"family":"Timsit","given":"Youri"}],"issued":{"date-parts":[["2016"]],"season":"26"}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">23,24</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">. Due to its
functional analogy with a sensor-motor
network, the r-protein network has been compared to a neural
network, at the
molecular level. Thus, it has been concluded that these tiny
but highly
conserved interfaces have been selected during evolution to
play a specific
role in inter-protein communication and they possess
interacting residues to
ensure information transfer from a protein to another. Thus,
these tiny
“molecular synapses" display a “necessary minimum” for
allosteric
transmission: a few conserved aromatic/charged amino acid
motifs (fig. 1). Moreover,
it is possible that these minimalist “molecular synapses”
reveal much more
general principles in molecular communication. Indeed, these
tiny interfaces,
which appear in their simplest expression in the ribosome
thanks to the spatial
constraints of ribosomal RNA (rRNA), could be ubiquitous in
macromolecular
complexes, but drowned out by a 'structural' background
involving other amino
acids for their stabilisation. <br>
</span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><br>
<span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB"><o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-family:Times;mso-bidi-font-family:Times;
mso-no-proof:yes"><!--[if gte vml 1]><v:shapetype id="_x0000_t75" coordsize="21600,21600"
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</v:shape><![endif]--><!--[if !vml]--><!--[endif]--></span><span
style="font-family:Times;
mso-bidi-font-family:Times"><img
src="cid:part1.308119B2.35B6ED9C@aragon.es" alt=""> <o:p></o:p></span></p>
<p class="MsoNormal"
style="margin-bottom:12.0pt;mso-pagination:none;mso-layout-grid-align:
none;text-autospace:none"><span
style="font-size:8.0pt;font-family:Times;
mso-bidi-font-family:Times;mso-bidi-font-weight:bold">Figure
1. Molecular
synapses and wires in the bacterial large subunit r-protein
network. The tiny
interfaces (the molecular synapses) between r-proteins are
represented by
surfaces </span><span
style="font-size:8.0pt;font-family:Times;mso-bidi-font-family:
Times"><o:p></o:p></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><span
style="font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB"> </span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><span
style="font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">Data from the
literature support our “vision of mind” that r-protein
networks could
contribute in both the ribosomal assembly and in the
“sensorimotor control” during
protein synthesis. Many experimental studies have indeed
shown indeed that ribosome
functional sites continually exchange and integrate
information during the
various steps of translation. As the numerous studies of the
Dinman group have
shown: “<i>an extensive network of
information flow through the ribosome</i>” during protein
biosynthesis </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"CBb0qWRt","properties":{"formattedCitation":"\\super
25\\uc0\\u8211{}32\\nosupersub{}","plainCitation":"25–32","noteIndex":0},"citationItems":[{"id":221,"uris":["http://zotero.org/users/local/yyYzumuD/items/9PUABGCZ"],"uri":["http://zotero.org/users/local/yyYzumuD/items/9PUABGCZ"],"itemData":{"id":221,"type":"article-journal","abstract":"Yeast
ribosomal proteins L11 and S18 form a dynamic intersubunit interaction called
the B1b/c bridge. Recent high resolution images of the ribosome have enabled
targeting of specific residues in this bridge to address how distantly
separated regions within the large and small subunits of the ribosome
communicate with each other. Mutations were generated in the L11 side of the
B1b/c bridge with a particular focus on disrupting the opposing charge motifs
that have previously been proposed to be involved in subunit ratcheting.
Mutants had wide-ranging effects on cellular viability and translational
fidelity, with the most pronounced phenotypes corresponding to amino acid
changes resulting in alterations of local charge properties. Chemical
protection studies of selected mutants revealed rRNA structural changes in both
the large and small subunits. In the large subunit rRNA, structural changes
mapped to Helices 39, 80, 82, 83, 84, and the peptidyltransferase center. In
the small subunit rRNA, structural changes were identified in helices 30 and
42, located between S18 and the decoding center. The rRNA structural changes
correlated with charge-specific alterations to the L11 side of the B1b/c
bridge. These analyses underscore the importance of the opposing charge
mechanism in mediating B1b/c bridge interactions and suggest an extensive
network of information exchange between distinct regions of the large and small
subunits.","container-title":"PloS
One","DOI":"10.1371/journal.pone.0020048","ISSN":"1932-6203","issue":"5","journalAbbreviation":"PLoS
ONE","language":"eng","note":"PMID:
21625514\nPMCID:
PMC3098278","page":"e20048","source":"PubMed","title":"An
extensive network of information flow through the B1b/c intersubunit bridge of
the yeast
ribosome","volume":"6","author":[{"family":"Rhodin","given":"Michael
H.
J."},{"family":"Dinman","given":"Jonathan
D."}],"issued":{"date-parts":[["2011"]]}}},{"id":62,"uris":["http://zotero.org/users/local/yyYzumuD/items/LNYPYWPZ"],"uri":["http://zotero.org/users/local/yyYzumuD/items/LNYPYWPZ"],"itemData":{"id":62,"type":"article-journal","abstract":"Although
the ribosome is mainly comprised of rRNA and many of its critical functions
occur through RNA-RNA interactions, distinct domains of ribosomal proteins also
participate in switching the ribosome between different
conformational/functional states. Prior studies demonstrated that two extended
domains of ribosomal protein L3 form an allosteric switch between the pre- and
post-translocational states. Missing was an explanation for how the movements
of these domains are communicated among the ribosome's functional centers.
Here, a third domain of L3 called the basic thumb, that protrudes roughly
perpendicular from the W-finger and is nestled in the center of a cagelike
structure formed by elements from three separate domains of the large subunit
rRNA is investigated. Mutagenesis of basically charged amino acids of the basic
thumb to alanines followed by detailed analyses suggests that it acts as a
molecular clamp, playing a role in allosterically communicating the ribosome's
tRNA occupancy status to the elongation factor binding region and the peptidyltransferase
center, facilitating coordination of their functions through the elongation
cycle. The observation that these mutations affected translational fidelity,
virus propagation and cell growth demonstrates how small structural changes at
the atomic scale can propagate outward to broadly impact the biology of
cell.","container-title":"Nucleic Acids
Research","DOI":"10.1093/nar/gkq641","ISSN":"1362-4962","issue":"21","journalAbbreviation":"Nucleic
Acids
Res.","language":"eng","note":"PMID:
20660012\nPMCID:
PMC2995063","page":"7800-7813","source":"PubMed","title":"A
molecular clamp ensures allosteric coordination of peptidyltransfer and ligand
binding to the ribosomal A-site","volume":"38","author":[{"family":"Meskauskas","given":"Arturas"},{"family":"Dinman","given":"Jonathan
D."}],"issued":{"date-parts":[["2010",11]]}}},{"id":73,"uris":["http://zotero.org/users/local/yyYzumuD/items/A8EW9X85"],"uri":["http://zotero.org/users/local/yyYzumuD/items/A8EW9X85"],"itemData":{"id":73,"type":"article-journal","abstract":"Ribosomes
transit between two conformational states, non-rotated and rotated, through the
elongation cycle. Here, we present evidence that an internal loop in the
essential yeast ribosomal protein rpL10 is a central controller of this process.
Mutations in this loop promote opposing effects on the natural equilibrium
between these two extreme conformational states. rRNA chemical modification
analyses reveals allosteric interactions involved in coordinating intersubunit
rotation originating from rpL10 in the core of the large subunit (LSU) through
both subunits, linking all the functional centers of the ribosome. Mutations
promoting rotational disequilibria showed catalytic, biochemical and
translational fidelity defects. An rpL3 mutation promoting opposing structural
and biochemical effects, suppressed an rpL10 mutant, re-establishing rotational
equilibrium. The rpL10 loop is also involved in Sdo1p recruitment, suggesting
that rotational status is important for ensuring late-stage maturation of the
LSU, supporting a model in which pre-60S subunits undergo a 'test drive' before
final maturation.","container-title":"Nucleic Acids
Research","DOI":"10.1093/nar/gkt1107","ISSN":"1362-4962","issue":"3","journalAbbreviation":"Nucleic
Acids Res.","language":"eng","note":"PMID:
24214990\nPMCID:
PMC3919601","page":"2049-2063","source":"PubMed","title":"Eukaryotic
rpL10 drives ribosomal rotation","volume":"42","author":[{"family":"Sulima","given":"Sergey
O."},{"family":"Gülay","given":"Suna
P."},{"family":"Anjos","given":"Margarida"},{"family":"Patchett","given":"Stephanie"},{"family":"Meskauskas","given":"Arturas"},{"family":"Johnson","given":"Arlen
W."},{"family":"Dinman","given":"Jonathan
D."}],"issued":{"date-parts":[["2014",2]]}}},{"id":76,"uris":["http://zotero.org/users/local/yyYzumuD/items/5A7HF8Y9"],"uri":["http://zotero.org/users/local/yyYzumuD/items/5A7HF8Y9"],"itemData":{"id":76,"type":"article-journal","abstract":"Chemical
modification was used to quantitatively determine the flexibility of nearly the
entire rRNA component of the yeast ribosome through 8 discrete stages of
translational elongation, revealing novel observations at the gross and
fine-scales. These include (i) the bulk transfer of energy through the
intersubunit bridges from the large to the small subunit after
peptidyltransfer, (ii) differences in the interaction of the sarcin ricin loop
with the two elongation factors and (iii) networked information exchange
pathways that may functionally facilitate intra- and intersubunit coordination,
including the 5.8S rRNA. These analyses reveal hot spots of fluctuations that
set the stage for large-scale conformational changes essential for
translocation and enable the first molecular dynamics simulation of an 80S
complex. Comprehensive datasets of rRNA base flexibilities provide a unique
resource to the structural biology community that can be computationally mined
to complement ongoing research toward the goal of understanding the dynamic
ribosome.","container-title":"Nucleic Acids Research","DOI":"10.1093/nar/gkx112","ISSN":"1362-4962","issue":"8","journalAbbreviation":"Nucleic
Acids
Res.","language":"eng","note":"PMID:
28334755\nPMCID: PMC5416885","page":"4958-4971","source":"PubMed","title":"Tracking
fluctuation hotspots on the yeast ribosome through the elongation
cycle","volume":"45","author":[{"family":"Gulay","given":"Suna
P."},{"family":"Bista","given":"Sujal"},{"family":"Varshney","given":"Amitabh"},{"family":"Kirmizialtin","given":"Serdal"},{"family":"Sanbonmatsu","given":"Karissa
Y."},{"family":"Dinman","given":"Jonathan
D."}],"issued":{"date-parts":[["2017"]],"season":"05"}}},{"id":286,"uris":["http://zotero.org/users/local/yyYzumuD/items/3PYC7GGJ"],"uri":["http://zotero.org/users/local/yyYzumuD/items/3PYC7GGJ"],"itemData":{"id":286,"type":"article-journal","abstract":"To
ensure accurate and rapid protein synthesis, nearby and distantly located
functional regions of the ribosome must dynamically communicate and coordinate
with one another through a series of information exchange networks. The ribosome
is approximately 2/3 rRNA and information should pass mostly through this
medium. Here, two viable mutants located in the peptidyltransferase center
(PTC) of yeast ribosomes were created using a yeast genetic system that enables
stable production of ribosomes containing only mutant rRNAs. The specific
mutants were C2820U (Escherichia coli C2452) and Psi2922C (E. coli U2554).
Biochemical and genetic analyses of these mutants suggest that they may trap
the PTC in the 'open' or aa-tRNA bound conformation, decreasing peptidyl-tRNA
binding. We suggest that these structural changes are manifested at the
biological level by affecting large ribosomal subunit biogenesis, ribosomal
subunit joining during initiation, susceptibility/resistance to peptidyltransferase
inhibitors, and the ability of ribosomes to properly decode termination codons.
These studies also add to our understanding of how information is transmitted
both locally and over long distances through allosteric networks of rRNA-rRNA
and rRNA-protein interactions.","container-title":"Nucleic
Acids
Research","DOI":"10.1093/nar/gkm1179","ISSN":"1362-4962","issue":"5","journalAbbreviation":"Nucleic
Acids Res.","language":"eng","note":"PMID:
18203742\nPMCID:
PMC2275155","page":"1497-1507","source":"PubMed","title":"rRNA
mutants in the yeast peptidyltransferase center reveal allosteric information
networks and mechanisms of drug
resistance","volume":"36","author":[{"family":"Rakauskaite","given":"Rasa"},{"family":"Dinman","given":"Jonathan
D."}],"issued":{"date-parts":[["2008",3]]}}},{"id":236,"uris":["http://zotero.org/users/local/yyYzumuD/items/25ZQKIZ6"],"uri":["http://zotero.org/users/local/yyYzumuD/items/25ZQKIZ6"],"itemData":{"id":236,"type":"article-journal","abstract":"Prior
studies identified allosteric information pathways connecting functional
centers in the large ribosomal subunit to the decoding center in the small
subunit through the B1a and B1b/c intersubunit bridges in yeast. In prokaryotes
a single SSU protein, uS13, partners with H38 (the A-site finger) and uL5 to
form the B1a and B1b/c bridges respectively. In eukaryotes, the SSU component
was split into 2 separate proteins during the course of evolution. One, also
known as uS13, participates in B1b/c bridge with uL5 in eukaryotes. The other,
called uS19 is the SSU partner in the B1a bridge with H38. Here, polyalanine
mutants of uS19 involved in the uS19/uS13 and the uS19/H38 interfaces were used
to elucidate the important amino acid residues involved in these intersubunit
communication pathways. Two key clusters of amino acids were identified: one
located at the junction between uS19 and uS13, and a second that appears to
interact with the distal tip of H38. Biochemical analyses reveal that these
mutations shift the ribosomal rotational equilibrium toward the unrotated
state, increasing ribosomal affinity for tRNAs in the P-site and for ternary
complex in the A-site, and inhibit binding of the translocase, eEF2. These
defects in turn affect specific aspects of translational fidelity. These findings
suggest that uS19 plays a critical role as a conduit of information exchange
between the large and small ribosomal subunits directly through the B1a, and
indirectly through the B1b/c
bridges.","container-title":"Translation (Austin,
Tex.)","DOI":"10.1080/21690731.2015.1117703","ISSN":"2169-074X","issue":"2","journalAbbreviation":"Translation
(Austin)","language":"eng","note":"PMID:
26824029\nPMCID: PMC4721500","page":"e1117703","source":"PubMed","title":"Ribosomal
protein uS19 mutants reveal its role in coordinating ribosome structure and
function","volume":"3","author":[{"family":"Bowen","given":"Alicia
M."},{"family":"Musalgaonkar","given":"Sharmishtha"},{"family":"Moomau","given":"Christine
A."},{"family":"Gulay","given":"Suna
P."},{"family":"Mirvis","given":"Mary"},{"family":"Dinman","given":"Jonathan
D."}],"issued":{"date-parts":[["2015",12]]}}},{"id":239,"uris":["http://zotero.org/users/local/yyYzumuD/items/WCU2VWXK"],"uri":["http://zotero.org/users/local/yyYzumuD/items/WCU2VWXK"],"itemData":{"id":239,"type":"article-journal","abstract":"During
translation, the two eukaryotic ribosomal subunits remain associated through 17
intersubunit bridges, five of which are eukaryote specific. These are mainly
localized to the peripheral regions and are believed to stabilize the structure
of the ribosome. The functional importance of these bridges remains largely
unknown. Here, the essentiality of the eukaryote-specific bridge eB12 has been
investigated. The main component of this bridge is ribosomal protein eL19 that
is composed of an N-terminal globular domain, a middle region, and a long
C-terminal </span><span style='font-size:10.0pt;line-height:150%;font-family:
"ＭＳ 明朝";mso-ascii-font-family:Times;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:
minor-fareast;mso-hansi-font-family:Times;mso-ansi-language:EN-GB'>α</span><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'>-helix. The analysis of deletion mutants demonstrated
that the globular domain and middle region of eL19 are essential for cell
viability, most likely functioning in ribosome assembly. The eB12 bridge,
formed by contacts between the C-terminal </span><span style='font-size:10.0pt;
line-height:150%;font-family:"ＭＳ 明朝";mso-ascii-font-family:Times;mso-fareast-font-family:
"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Times;
mso-ansi-language:EN-GB'>α</span><span lang=EN-GB style='font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB'>-helix of eL19 and
18S rRNA in concert with additional stabilizing interactions involving either
eS7 or uS17, is dispensable for viability. Nevertheless, eL19 mutants impaired
in eB12 bridge formation displayed slow growth phenotypes, altered
sensitivity/resistance to translational inhibitors, and enhanced hyperosmotic
stress tolerance. Biochemical analyses determined that the eB12 bridge
contributes to the stability of ribosome subunit interactions in vitro. 60S
subunits containing eL19 variants defective in eB12 bridge formation failed to
form 80S ribosomes regardless of Mg(2+) concentration. The reassociation of 40S
and mutant 60S subunits was markedly improved in the presence of deacetylated
tRNA, emphasizing the importance of tRNAs during the subunit association. We
propose that the eB12 bridge plays an important role in subunit joining and in
optimizing ribosome
functionality.","container-title":"Journal of Molecular
Biology","DOI":"10.1016/j.jmb.2016.03.023","ISSN":"1089-8638","issue":"10
Pt B","journalAbbreviation":"J. Mol.
Biol.","language":"eng","note":"PMID:
27038511\nPMCID: PMC4884501","page":"2203-2216","source":"PubMed","title":"The
Functional Role of eL19 and eB12 Intersubunit Bridge in the Eukaryotic
Ribosome","volume":"428","author":[{"family":"Kisly","given":"Ivan"},{"family":"Gulay","given":"Suna
P."},{"family":"Mäeorg","given":"Uno"},{"family":"Dinman","given":"Jonathan
D."},{"family":"Remme","given":"Jaanus"},{"family":"Tamm","given":"Tiina"}],"issued":{"date-parts":[["2016",5,22]]}}},{"id":227,"uris":["http://zotero.org/users/local/yyYzumuD/items/LINATLGV"],"uri":["http://zotero.org/users/local/yyYzumuD/items/LINATLGV"],"itemData":{"id":227,"type":"article-journal","abstract":"Ribosomal
protein L2 is a core element of the large subunit that is highly conserved
among all three kingdoms. L2 contacts almost every domain of the large subunit
rRNA and participates in an intersubunit bridge with the small subunit rRNA. It
contains a solvent-accessible globular domain that interfaces with the solvent
accessible side of the large subunit that is linked through a bridge to an
extension domain that approaches the peptidyltransferase center. Here,
screening of randomly generated library of yeast RPL2A alleles identified three
translationally defective mutants, which could be grouped into two classes. The
V48D and L125Q mutants map to the globular domain. They strongly affect
ribosomal A-site associated functions, peptidyltransferase activity and subunit
joining. H215Y, located at the tip of the extended domain interacts with Helix
93. This mutant specifically affects peptidyl-tRNA binding and
peptidyltransferase activity. Both classes affect rRNA structure far away from
the protein in the A-site of the peptidyltransferase center. These findings
suggest that defective interactions with Helix 55 and with the Helix 65-66
structure may indicate a certain degree of flexibility in L2 in the neck region
between the two other domains, and that this might help to coordinate
tRNA-ribosome interactions.","container-title":"Nucleic
Acids
Research","DOI":"10.1093/nar/gkn034","ISSN":"1362-4962","issue":"6","journalAbbreviation":"Nucleic
Acids
Res.","language":"eng","note":"PMID:
18263608\nPMCID: PMC2330241","page":"1826-1835","source":"PubMed","title":"Structure/function
analysis of yeast ribosomal protein
L2","volume":"36","author":[{"family":"Meskauskas","given":"Arturas"},{"family":"Russ","given":"Johnathan
R."},{"family":"Dinman","given":"Jonathan
D."}],"issued":{"date-parts":[["2008",4]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">25–32</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">. For example, several
studies have also demonstrated
long-range signalling between the decoding centre that
monitors the correct
geometry of the codon-anticodon and other distant sites such
as the Sarcin
Ricin Loop (SRL) or the E-tRNA site </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"rOyj5yiB","properties":{"formattedCitation":"\\super
15,33\\nosupersub{}","plainCitation":"15,33","noteIndex":0},"citationItems":[{"id":56,"uris":["http://zotero.org/users/local/yyYzumuD/items/9H63AUTZ"],"uri":["http://zotero.org/users/local/yyYzumuD/items/9H63AUTZ"],"itemData":{"id":56,"type":"article-journal","abstract":"The
sequential addition of amino acids to a growing polypeptide chain is carried
out by the ribosome in a complicated multistep process called the elongation
cycle. It involves accurate selection of each aminoacyl tRNA as dictated by the
mRNA codon, catalysis of peptide bond formation, and movement of the tRNAs and
mRNA through the ribosome. The process requires the GTPase factors elongation
factor Tu (EF-Tu) and EF-G. Not surprisingly, large conformational changes in
both the ribosome and its tRNA substrates occur throughout protein elongation.
Major advances in our understanding of the elongation cycle have been made in
the past few years as a result of high-resolution crystal structures that
capture various states of the process, as well as biochemical and computational
studies.","container-title":"Annual Review of
Biochemistry","DOI":"10.1146/annurev-biochem-113009-092313","ISSN":"1545-4509","journalAbbreviation":"Annu.
Rev. Biochem.","language":"eng","note":"PMID:
23746255","page":"203-236","source":"PubMed","title":"Structural
basis of the translational elongation
cycle","volume":"82","author":[{"family":"Voorhees","given":"Rebecca
M."},{"family":"Ramakrishnan","given":"V."}],"issued":{"date-parts":[["2013"]]}}},{"id":59,"uris":["http://zotero.org/users/local/yyYzumuD/items/23KFGRQ7"],"uri":["http://zotero.org/users/local/yyYzumuD/items/23KFGRQ7"],"itemData":{"id":59,"type":"article-journal","abstract":"The
faithful and rapid translation of genetic information into peptide sequences is
an indispensable property of the ribosome. The mechanistic understanding of
strategies used by the ribosome to achieve both speed and fidelity during
translation results from nearly a half century of biochemical and structural
studies. Emerging from these studies is the common theme that the ribosome uses
local as well as remote conformational switches to govern induced-fit
mechanisms that ensure accuracy in codon recognition during both tRNA selection
and translation
termination.","container-title":"Cell","DOI":"10.1016/j.cell.2009.01.036","ISSN":"1097-4172","issue":"4","journalAbbreviation":"Cell","language":"eng","note":"PMID:
19239893\nPMCID: PMC3691815","page":"746-762","source":"PubMed","title":"Fidelity
at the molecular level: lessons from protein
synthesis","title-short":"Fidelity at the molecular
level","volume":"136","author":[{"family":"Zaher","given":"Hani
S."},{"family":"Green","given":"Rachel"}],"issued":{"date-parts":[["2009",2,20]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">15,33</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">. R-proteins of the
ribosomal tunnel also play an
active role in the regulation of protein synthesis and
co-translational folding
</span><!--[if supportFields]><span lang=EN-GB style='font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"m8XRZnK8","properties":{"formattedCitation":"\\super
34,35\\nosupersub{}","plainCitation":"34,35","noteIndex":0},"citationItems":[{"id":65,"uris":["http://zotero.org/users/local/yyYzumuD/items/G3GTPMW8"],"uri":["http://zotero.org/users/local/yyYzumuD/items/G3GTPMW8"],"itemData":{"id":65,"type":"article-journal","abstract":"As
the nascent polypeptide chain is being synthesized, it passes through a tunnel
within the large ribosomal subunit. Interaction between the nascent polypeptide
chain and the ribosomal tunnel can modulate the translation rate and induce
translational stalling to regulate gene expression. In this article, we
highlight recent structural insights into how the nascent polypeptide chain,
either alone or in cooperation with co-factors, can interact with components of
the ribosomal tunnel to regulate translation via inactivating the
peptidyltransferase center of the ribosome and inducing ribosome
stalling.","container-title":"Current Opinion in Structural
Biology","DOI":"10.1016/j.sbi.2016.01.008","ISSN":"1879-033X","journalAbbreviation":"Curr.
Opin. Struct. Biol.","language":"eng","note":"PMID:
26859868","page":"123-133","source":"PubMed","title":"Translation
regulation via nascent polypeptide-mediated ribosome stalling","volume":"37","author":[{"family":"Wilson","given":"Daniel
N."},{"family":"Arenz","given":"Stefan"},{"family":"Beckmann","given":"Roland"}],"issued":{"date-parts":[["2016",4]]}}},{"id":67,"uris":["http://zotero.org/users/local/yyYzumuD/items/ULMARGUG"],"uri":["http://zotero.org/users/local/yyYzumuD/items/ULMARGUG"],"itemData":{"id":67,"type":"article-journal","abstract":"Cells
face a constant challenge as they produce new proteins. The newly synthesized
polypeptides must be folded properly to avoid aggregation. If proteins do
misfold, they must be cleared to maintain a functional and healthy proteome.
Recent work is revealing the complex mechanisms that work cotranslationally to
ensure protein quality control during biogenesis at the ribosome. Indeed, the
ribosome is emerging as a central hub in coordinating these processes,
particularly in sensing the nature of the nascent protein chain, recruiting
protein folding and translocation components, and integrating mRNA and nascent
chain quality control. The tiered and complementary nature of these
decision-making processes confers robustness and fidelity to protein
homeostasis during protein
synthesis.","container-title":"Molecular
Cell","DOI":"10.1016/j.molcel.2013.01.020","ISSN":"1097-4164","issue":"3","journalAbbreviation":"Mol.
Cell","language":"eng","note":"PMID:
23395271\nPMCID: PMC3593112","page":"411-421","source":"PubMed","title":"The
ribosome as a hub for protein quality
control","volume":"49","author":[{"family":"Pechmann","given":"Sebastian"},{"family":"Willmund","given":"Felix"},{"family":"Frydman","given":"Judith"}],"issued":{"date-parts":[["2013",2,7]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">34,35</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">. Ribosomes also
perceive each other through quality
sensor of collided ribosomes in eukaryotes </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"JBCxacSY","properties":{"formattedCitation":"\\super
36\\nosupersub{}","plainCitation":"36","noteIndex":0},"citationItems":[{"id":749,"uris":["http://zotero.org/users/local/yyYzumuD/items/XHJNX6AC"],"uri":["http://zotero.org/users/local/yyYzumuD/items/XHJNX6AC"],"itemData":{"id":749,"type":"article-journal","abstract":"Aberrantly
slow translation elicits quality control pathways initiated by the ubiquitin
ligase ZNF598. How ZNF598 discriminates physiologic from pathologic translation
complexes and ubiquitinates stalled ribosomes selectively is unclear. Here, we
find that the minimal unit engaged by ZNF598 is the collided di-ribosome, a
molecular species that arises when a trailing ribosome encounters a slower
leading ribosome. The collided di-ribosome structure reveals an extensive
40S-40S interface in which the ubiquitination targets of ZNF598 reside. The
paucity of 60S interactions allows for different ribosome rotation states,
explaining why ZNF598 recognition is indifferent to how the leading ribosome
has stalled. The use of ribosome collisions as a proxy for stalling allows the
degree of tolerable slowdown to be tuned by the initiation rate on that mRNA;
hence, the threshold for triggering quality control is substrate specific.
These findings illustrate how higher-order ribosome architecture can be
exploited by cellular factors to monitor translation
status.","container-title":"Molecular
Cell","DOI":"10.1016/j.molcel.2018.08.037","ISSN":"1097-4164","issue":"3","journalAbbreviation":"Mol
Cell","language":"eng","note":"PMID:
30293783\nPMCID:
PMC6224477","page":"469-481.e7","source":"PubMed","title":"ZNF598
Is a Quality Control Sensor of Collided Ribosomes","volume":"72","author":[{"family":"Juszkiewicz","given":"Szymon"},{"family":"Chandrasekaran","given":"Viswanathan"},{"family":"Lin","given":"Zhewang"},{"family":"Kraatz","given":"Sebastian"},{"family":"Ramakrishnan","given":"V."},{"family":"Hegde","given":"Ramanujan
S."}],"issued":{"date-parts":[["2018",11,1]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">36</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">. In addition, the ribosomes synchronize many
complex movements during
the translation cycles </span><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"KBK07CCi","properties":{"formattedCitation":"\\super
37\\uc0\\u8211{}39\\nosupersub{}","plainCitation":"37–39","noteIndex":0},"citationItems":[{"id":70,"uris":["http://zotero.org/users/local/yyYzumuD/items/LA4G63CC"],"uri":["http://zotero.org/users/local/yyYzumuD/items/LA4G63CC"],"itemData":{"id":70,"type":"article-journal","abstract":"Protein
synthesis is inherently a dynamic process, requiring both small-scale and
large-scale movements of tRNA and mRNA. It has long been suspected that these
movements might be coupled to conformational changes in the ribosome, and in its
RNA moieties in particular. Recently, the nature of ribosome structural
dynamics has begun to emerge from a combination of approaches, most notably
cryo-EM, X-ray crystallography, and FRET. Ribosome movement occurs both on a
grand scale, as in the intersubunit rotational movements that are coupled to
tRNA-mRNA translocation, and in intricate localized rearrangements such as
those that accompany codon-anticodon recognition and peptide bond formation. In
spite of much progress, our understanding of the mechanics of translation is
now beset with countless new questions, reflecting the vast molecular
architecture of the ribosome
itself.","container-title":"Current Opinion in Chemical
Biology","DOI":"10.1016/j.cbpa.2008.08.037","ISSN":"1879-0402","issue":"6","journalAbbreviation":"Curr
Opin Chem
Biol","language":"eng","note":"PMID:
18848900\nPMCID:
PMC3923522","page":"674-683","source":"PubMed","title":"Structural
dynamics of the
ribosome","volume":"12","author":[{"family":"Korostelev","given":"Andrei"},{"family":"Ermolenko","given":"Dmitri
N."},{"family":"Noller","given":"Harry
F."}],"issued":{"date-parts":[["2008",12]]}}},{"id":752,"uris":["http://zotero.org/users/local/yyYzumuD/items/6TP77B74"],"uri":["http://zotero.org/users/local/yyYzumuD/items/6TP77B74"],"itemData":{"id":752,"type":"article-journal","abstract":"Major
centers of motion in the rRNAs of Thermus thermophilus are identified by
alignment of crystal structures of EF-G bound and EF-G unbound ribosomal
subunits. Small rigid helices upstream of these 'pivots' are aligned, thereby
decoupling their motion from global rearrangements. Of the 21 pivots found, six
are observed in the large subunit rRNA and 15 in the small subunit rRNA.
Although the magnitudes of motion differ, with only minor exceptions equivalent
pivots are seen in comparisons of Escherichia coli structures and one
Saccharomyces cerevisiae structure pair. The pivoting positions are typically
associated with structurally weak motifs such as non-canonical, primarily U-G
pairs, bulge loops and three-way junctions. Each pivot is typically in direct
physical contact with at least one other in the set and often several others.
Moving helixes include rRNA segments in contact with the tRNA, intersubunit
bridges and helices 28, 32 and 34 of the small subunit. These helices are
envisioned to form a network. EF-G rearrangement would then provide directional
control of this network propagating motion from the tRNA to the intersubunit
bridges to the head swivel or along the same path backward.","container-title":"Nucleic
Acids
Research","DOI":"10.1093/nar/gkv289","ISSN":"1362-4962","issue":"9","journalAbbreviation":"Nucleic
Acids Res","language":"eng","note":"PMID:
25870411\nPMCID:
PMC4482067","page":"4640-4649","source":"PubMed","title":"Major
centers of motion in the large ribosomal
RNAs","volume":"43","author":[{"family":"Paci","given":"Maxim"},{"family":"Fox","given":"George
E."}],"issued":{"date-parts":[["2015",5,19]]}}},{"id":755,"uris":["http://zotero.org/users/local/yyYzumuD/items/LFU79JAW"],"uri":["http://zotero.org/users/local/yyYzumuD/items/LFU79JAW"],"itemData":{"id":755,"type":"article-journal","abstract":"Structural
centers of motion (pivot points) in the ribosome have recently been identified
by measurement of conformational changes in rRNA resulting from EF-G GTP
hydrolysis. This series of measurements is extended here to the ribosome's
interactions with the cofactor EF-Tu. Four recent EF-Tu bound ribosome
structures were compared to unbound structures. A total of 16 pivots were
identified, of which 4 are unique to the EF-Tu interaction. Pivots in the
GTPase associated center and the sarcin-ricin loop omitted previously, are
found to be mobile in response to both EF-Tu and EF-G binding. Pivots in the
intersubunit bridge rRNAs are found to be cofactor specific. Head swiveling
motions in the small subunit are observed in the EF-Tu bound structures that
were trapped post GTP hydrolysis. As in the case of pivots associated with
EF-G, the additional pivots described here are associated with weak points in
the rRNA structures such as non-canonical pairs and bulge loops. The combined
set of pivots should be regarded as a minimal set. Only several states
available to the ribosome have been presented in this work. Future, precise
crystal structures in conjunction with experimental data will likely show
additional functional pivoting elements in the
rRNA.","container-title":"RNA
biology","DOI":"10.1080/15476286.2015.1114204","ISSN":"1555-8584","issue":"5","journalAbbreviation":"RNA
Biol","language":"eng","note":"PMID:
26786136\nPMCID:
PMC4962796","page":"524-530","source":"PubMed","title":"Centers
of motion associated with EF-Tu binding to the
ribosome","volume":"13","author":[{"family":"Paci","given":"Maxim"},{"family":"Fox","given":"George
E."}],"issued":{"date-parts":[["2016",5,3]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">37–39</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">. The recent
discoveries of “ribosome heterogeneity” </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"aq9FWUrj","properties":{"formattedCitation":"\\super
40\\nosupersub{}","plainCitation":"40","noteIndex":0},"citationItems":[{"id":79,"uris":["http://zotero.org/users/local/yyYzumuD/items/FXLH8VQ3"],"uri":["http://zotero.org/users/local/yyYzumuD/items/FXLH8VQ3"],"itemData":{"id":79,"type":"article-journal","abstract":"The
ribosome has recently transitioned from being viewed as a passive,
indiscriminate machine to a more dynamic macromolecular complex with
specialized roles in the cell. Here, we discuss the historical milestones from
the discovery of the ribosome itself to how this ancient machinery has gained
newfound appreciation as a more regulatory participant in the central dogma of
gene expression. The first emerging examples of direct changes in ribosome
composition at the RNA and protein level, coupled with an increased awareness
of the role individual ribosomal components play in the translation of specific
mRNAs, is opening a new field of study centered on ribosome-mediated control of
gene regulation. In this Perspective, we discuss our current understanding of
the known functions for ribosome heterogeneity, including specialized
translation of individual transcripts, and its implications for the regulation
and expression of key gene regulatory networks. In addition, we suggest what
the crucial next steps are to ascertain the extent of ribosome heterogeneity
and specialization and its importance for regulation of the proteome within
subcellular space, across different cell types, and during multi-cellular
organismal development.","container-title":"Molecular
Cell","DOI":"10.1016/j.molcel.2018.07.018","ISSN":"1097-4164","issue":"3","journalAbbreviation":"Mol.
Cell","language":"eng","note":"PMID:
30075139\nPMCID:
PMC6092941","page":"364-374","source":"PubMed","title":"The
Discovery of Ribosome Heterogeneity and Its Implications for Gene Regulation
and Organismal
Life","volume":"71","author":[{"family":"Genuth","given":"Naomi
R."},{"family":"Barna","given":"Maria"}],"issued":{"date-parts":[["2018"]],"season":"02"}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">40</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB"> also significantly expands the complexity of
the possible ribosome’s
network topologies </span><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"ilTzzd0c","properties":{"formattedCitation":"\\super
41\\nosupersub{}","plainCitation":"41","noteIndex":0},"citationItems":[{"id":82,"uris":["http://zotero.org/users/local/yyYzumuD/items/IWK4Y7EE"],"uri":["http://zotero.org/users/local/yyYzumuD/items/IWK4Y7EE"],"itemData":{"id":82,"type":"article-journal","abstract":"\"Specialized
ribosomes\" is a topic of intense debate and research whose provenance can
be traced to the earliest days of molecular biology. Here, the history of this
idea is reviewed, and critical literature in which the specialized ribosomes
have come to be presently defined is discussed. An argument supporting the
evolution of a variety of ribosomes with specialized functions as a consequence
of selective pressures acting on a near-infinite set of possible ribosomes is
presented, leading to a discussion of how this may also serve as a biological
buffering mechanism. The possible relationship between specialized ribosomes
and human health is explored. A set of criteria and possible approaches are
also presented to help guide the definitive identification of
\"specialized\" ribosomes, and this is followed by a discussion of
how synthetic biology approaches might be used to create new types of special
ribosomes.","container-title":"Journal of Molecular Biology","DOI":"10.1016/j.jmb.2015.12.021","ISSN":"1089-8638","issue":"10
Pt B","journalAbbreviation":"J. Mol.
Biol.","language":"eng","note":"PMID:
26764228\nPMCID: PMC4884523","page":"2186-2194","source":"PubMed","title":"Pathways
to Specialized Ribosomes: The Brussels Lecture","title-short":"Pathways
to Specialized
Ribosomes","volume":"428","author":[{"family":"Dinman","given":"Jonathan
D."}],"issued":{"date-parts":[["2016",5,22]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">41</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB"> and open new perspective on
“network plasticity” that could also play a role its
behavioural richness. <o:p></o:p></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><span
style="font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">A recent
interdisciplinary study with my mathematician colleagues
Daniel Bennequin and
Grégoire Segeant-Perthuis has shown how r-protein networks
have evolved toward
a growing complexity through the coevolution of the
r-protein extensions and
the increasing number of connexions </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"2Ru1Kl5n","properties":{"formattedCitation":"\\super
42\\nosupersub{}","plainCitation":"42","noteIndex":0},"citationItems":[{"id":766,"uris":["http://zotero.org/users/local/yyYzumuD/items/PTYCE9KT"],"uri":["http://zotero.org/users/local/yyYzumuD/items/PTYCE9KT"],"itemData":{"id":766,"type":"article-journal","abstract":"To
perform an accurate protein synthesis, ribosomes accomplish complex tasks
involving the long-range communication between its functional centres such as
the peptidyl transfer centre, the tRNA bindings sites and the peptide exit
tunnel. How information is transmitted between these sites remains one of the
major challenges in current ribosome research. Many experimental studies have
revealed that some r-proteins play essential roles in remote communication and
the possible involvement of r-protein networks in these processes have been
recently proposed. Our phylogenetic, structural and mathematical study reveals
that of the three kingdom's r-protein networks converged towards non-random
graphs where r-proteins collectively coevolved to optimize interconnection
between functional centres. The massive acquisition of conserved aromatic
residues at the interfaces and along the extensions of the newly connected
eukaryotic r-proteins also highlights that a strong selective pressure acts on
their sequences probably for the formation of new allosteric pathways in the
network.","container-title":"Scientific
Reports","DOI":"10.1038/s41598-020-80194-4","ISSN":"2045-2322","issue":"1","journalAbbreviation":"Sci
Rep","language":"eng","note":"PMID:
33436806\nPMCID: PMC7804294","page":"625","source":"PubMed","title":"Evolution
of ribosomal protein network
architectures","volume":"11","author":[{"family":"Timsit","given":"Youri"},{"family":"Sergeant-Perthuis","given":"Grégoire"},{"family":"Bennequin","given":"Daniel"}],"issued":{"date-parts":[["2021",1,12]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">42</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">. This study revealed that network expansion is
produced by the
collective (co)-evolution of r-proteins leading to an
asymmetrical evolution of
the two subunits. Furthermore, graph theory showed that the
network evolution
did not occur at random: each new occurring extensions and
connections
gradually relates functional modules and places the
functional centres in
central positions of the network. The strong selective
pressure that is also
expressed at the amino acid acquisition links the network
architectures and the
r-protein phylogeny thus suggesting that the networks have
gradually evolved to
sophisticated allosteric pathways. The congruence between
independent
evolutionary traits indicates that the network architectures
evolved to relate
and optimize the information spread between functional
modules (fig. 2). In
summary, graph theory, without knowing the function of the
ribosome, can
blindly detect the central functional centres of the
ribosome. Conversely,
ribosomes have learned graph theory during evolution, by
placing the PTC and
important functional centres at nodes corresponding to the
maximum centrality
of the network.</span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><br>
<span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB"><o:p></o:p></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><span
style="font-family:Times;
mso-bidi-font-family:Times"><img
src="cid:part2.EAF6D293.A8E4653E@aragon.es" alt=""></span><br>
<span style="font-size:10.0pt;line-height:
150%;font-family:Times;mso-no-proof:yes"><!--[endif]--></span><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB"><o:p></o:p></span></p>
<p class="MsoNormal"
style="margin-bottom:12.0pt;mso-pagination:none;mso-layout-grid-align:
none;text-autospace:none"><b><span
style="font-size:8.0pt;font-family:Times;
mso-bidi-font-family:Times">Figure 2. r-protein and
functional centres networks in the large subunit of the
eukaryotic ribosome. </span></b><span
style="font-size:8.0pt;font-family:Times;
mso-bidi-font-family:Times">The r-proteins and their
extensions are represented
according to their evolutionary status. Universal (common to
bacteria, archaea
and eukarya): red; Archaea: cyan; Eukarya: yellow. Lines
between two circles
symbolize an interaction between two globular domains. The
colours of the lines
follow the code for the evolutionary status described above,
except for eukarya
specific connection that are represented with black lines,
for clarity. “N” or
“C” indicate if the seg or mix are N-terminal or C-terminal
extensions. NC
indicates proteins without a globular domain (uS14, eL29,
eS30, eL37 and eL39).
Functional sites (PTC, Tunnel, tRNAs and mRNA) are
represented in light blue.
The names of bacterial proteins which, by convergence,
occupy a position
similar to that of Eukaryotic or Archaeal r-proteins, are
shown in blue below
the circles. <o:p></o:p></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><span
style="font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB"> </span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><span
style="font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">Moreover, a network
archaeology study has also revealed the existence of a
universal network, that
consists of 49 strictly conserved connections that was
probably present before
the radiation of the bacteria and archaea </span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_ITEM CSL_CITATION
{"citationID":"D0rOLRD4","properties":{"formattedCitation":"\\super
43\\nosupersub{}","plainCitation":"43","noteIndex":0},"citationItems":[{"id":248,"uris":["http://zotero.org/users/local/yyYzumuD/items/VPW9GF7K"],"uri":["http://zotero.org/users/local/yyYzumuD/items/VPW9GF7K"],"itemData":{"id":248,"type":"article-journal","abstract":"Biologists
used to draw schematic \"universal\" trees of life as metaphors
illustrating the history of life. It is indeed a priori possible to construct
an organismal tree connecting the three major domains of ribosome encoding
organisms: Archaea, Bacteria and Eukarya, since they originated by cell
division from LUCA. Several universal trees based on ribosomal RNA sequence
comparisons proposed at the end of the last century are still widely used,
although some of their main features have been challenged by subsequent
analyses. Several authors have proposed to replace the traditional universal
tree with a ring of life, whereas others have proposed more recently to include
viruses as new domains. These proposals are misleading, suggesting that
endosymbiosis can modify the shape of a tree or that viruses originated from
the last universal common ancestor (LUCA). I propose here an updated version of
Woese's universal tree that includes several rootings for each domain and
internal branching within domains that are supported by recent phylogenomic
analyses of domain specific proteins. The tree is rooted between Bacteria and
Arkarya, a new name proposed for the clade grouping Archaea and Eukarya. A
consensus version, in which each of the three domains is unrooted, and a
version in which eukaryotes emerged within archaea are also presented. This
last scenario assumes the transformation of a modern domain into another, a
controversial evolutionary pathway. Viruses are not indicated in these trees
but are intrinsically present because they infect the tree from its roots to
its leaves. Finally, I present a detailed tree of the domain Archaea, proposing
the sub-phylum neo-Euryarchaeota for the monophyletic group of euryarchaeota
containing DNA gyrase. These trees, that will be easily updated as new data
become available, could be useful to discuss controversial scenarios regarding
early life evolution.","container-title":"Frontiers in
Microbiology","DOI":"10.3389/fmicb.2015.00717","ISSN":"1664-302X","journalAbbreviation":"Front
Microbiol","language":"eng","note":"PMID:
26257711\nPMCID: PMC4508532","page":"717","source":"PubMed","title":"The
universal tree of life: an update","title-short":"The
universal tree of life","volume":"6","author":[{"family":"Forterre","given":"Patrick"}],"issued":{"date-parts":[["2015"]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">43</span></sup><!--[if supportFields]><span lang=EN-GB style='font-size:
10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB'><span
style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:EN-GB"
lang="EN-GB">. This primordial network is much more
developed in the small ribosomal
subunit suggesting that the large subunit network complexity
developed in later
evolutionary stages. These findings therefore suggest that
LUCA already
possessed such type of molecular networks, with long wires
and tiny interfaces.
Interestingly, these networks also mix the i-systems of
rRNA and aromatic
amino acids of proteins for forming conserved structural
motifs probably
involved in a still unknown mechanism of signal transduction
(probably
involving electron or charge transfer). It is therefore
possible that this
ancestral mode of communication has then not only evolved in
modern ribosomes
but in other macromolecular systems for information transfer
and processing.
These results therefore suggest that the ribosome opens a
window on the first
information processing networks, which appeared at the
origin of life. They probably
diverged towards other cell systems that have been compared
to brains such as
the multiple nano-brains. These works provide the molecular
basis to decipher
how non-neural unicellular organisms may display complex
behaviours such as
associative learning and decision-making</span><!--[if supportFields]><span
lang=EN-GB style='font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB'><span style='mso-element:field-begin'></span> ADDIN
ZOTERO_ITEM CSL_CITATION
{"citationID":"XxN9wtSg","properties":{"formattedCitation":"\\super
1,2,44\\nosupersub{}","plainCitation":"1,2,44","noteIndex":0},"citationItems":[{"id":580,"uris":["http://zotero.org/users/local/yyYzumuD/items/JHKLLW8V"],"uri":["http://zotero.org/users/local/yyYzumuD/items/JHKLLW8V"],"itemData":{"id":580,"type":"article-journal","abstract":"Understanding
the nature of life has always been a fundamental objective of human knowledge.
It is no wonder that biology, as the science of life, together with physics,
has traditionally been the discipline that has generated the deepest
philosophical and social repercussions. In our time, the major achievements in
bioinformatics, systems biology, and \"omic\" fields (genomics,
proteomics, metabolomics, etc.) have not only spurred a new biotechnological
and biomedical 'postindustrial revolution', but they have also disclosed an
intriguing molecular panorama of biological organization that invites us to
reinterpret central themes of philosophy in the light of the new knowledge.
Essential tenets of phenomenology may take an intriguing new turn when
contemplated from these new biological perspectives: Does the living cell
instantiate a unique biomolecular way of being in the world? How is life
self-produced in continuous communication with the surrounding world? How can
the incessant flows of mass, energy and information inherent of embodiment be
coherently harnessed across billions of cellular individuals? In this paper,
based on the latest developments in cellular signaling, we will discuss the
dynamic intertwining between self-production and communication that
characterizes life at the prokaryotic, eukaryotic, organismic, and social
levels of organization. An in-depth analysis of the particular transcriptional
responses of a bacterium (Escherichia coli K-12 strain), taking as a model
system, will follow. It is the creation, transmission and reception of signals
which, in all instances, provides guidance and orientation to the inner
self-production activities of the living agent and connects it with the world.
Transitions to new levels of organization are marked by the emergence of new
forms of communication, embedded in the correspondingly augmented life-cycles
of the more complex entities. As will be argued here, the ascending complexity
of life is always information-based and recapitulates level after level, a
successful \"informational formula\" for being in the world. The
phenomenological basis for the naturalization of cognition has moved from the
biological to a new scientific arena: informational. The philosophical notion
of being-in-the-world (Dasein; Heidegger) is shown to be completely compatible
with the latest advances in biology and information
science.","container-title":"Progress in Biophysics and
Molecular
Biology","DOI":"10.1016/j.pbiomolbio.2015.07.002","ISSN":"1873-1732","issue":"3","journalAbbreviation":"Prog
Biophys Mol Biol","language":"eng","note":"PMID:
26169771","page":"469-480","source":"PubMed","title":"How
the living is in the world: An inquiry into the informational choreographies of
life","title-short":"How the living is in the
world","volume":"119","author":[{"family":"Marijuán","given":"Pedro
C."},{"family":"Navarro","given":"Jorge"},{"family":"Moral","given":"Raquel","non-dropping-particle":"del"}],"issued":{"date-parts":[["2015",12]]}}},{"id":6553,"uris":["http://zotero.org/users/local/yyYzumuD/items/N2GE2EJL"],"uri":["http://zotero.org/users/local/yyYzumuD/items/N2GE2EJL"],"itemData":{"id":6553,"type":"article-journal","abstract":"How
can single cells without nervous systems perform complex behaviours such as
habituation, associative learning and decision making, which are considered the
hallmark of animals with a brain? Are there molecular systems that underlie
cognitive properties equivalent to those of the brain? This review follows the
development of the idea of molecular brains from Darwin’s “root brain
hypothesis”, through bacterial chemotaxis, to the recent discovery of
neuron-like r-protein networks in the ribosome. By combining a structural
biology view with a Bayesian brain approach, this review explores the
evolutionary labyrinth of information processing systems across scales.
Ribosomal protein networks open a window into what were probably the earliest
signalling systems to emerge before the radiation of the three kingdoms. While
ribosomal networks are characterised by long-lasting interactions between their
protein nodes, cell signalling networks are essentially based on transient
interactions. As a corollary, while signals propagated in persistent networks
may be ephemeral, networks whose interactions are transient constrain signals
diffusing into the cytoplasm to be durable in time, such as post-translational
modifications of proteins or second messenger synthesis. The duration and
nature of the signals, in turn, implies different mechanisms for the
integration of multiple signals and decision making. Evolution then reinvented
networks with persistent interactions with the development of nervous systems
in metazoans. Ribosomal protein networks and simple nervous systems display
architectural and functional analogies whose comparison could suggest scale
invariance in information processing. At the molecular level, the significant
complexification of eukaryotic ribosomal protein networks is associated with a
burst in the acquisition of new conserved aromatic amino acids. Knowing that
aromatic residues play a critical role in allosteric receptors and channels,
this observation suggests a general role of </span><span style='font-size:10.0pt;
line-height:150%;font-family:"ＭＳ 明朝";mso-ascii-font-family:Times;mso-fareast-font-family:
"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Times;
mso-ansi-language:EN-GB'>π</span><span lang=EN-GB style='font-size:10.0pt;
line-height:150%;font-family:Times;mso-ansi-language:EN-GB'> systems and their
interactions with charged amino acids in multiple signal integration and
information processing. We think that these findings may provide the molecular
basis for designing future computers with organic processors.","container-title":"International
Journal of Molecular
Sciences","DOI":"10.3390/ijms222111868","issue":"21","language":"en","note":"number:
21\npublisher: Multidisciplinary Digital Publishing Institute","page":"11868","source":"www.mdpi.com","title":"Towards
the Idea of Molecular
Brains","volume":"22","author":[{"family":"Timsit","given":"Youri"},{"family":"Grégoire","given":"Sergeant-Perthuis"}],"issued":{"date-parts":[["2021",1]]}}},{"id":585,"uris":["http://zotero.org/users/local/yyYzumuD/items/23AL4KX8"],"uri":["http://zotero.org/users/local/yyYzumuD/items/23AL4KX8"],"itemData":{"id":585,"type":"article-journal","abstract":"The
central nervous system (CNS) underlies memory, perception, decision-making, and
behavior in numerous organisms. However, neural networks have no monopoly on
the signaling functions that implement these remarkable algorithms. It is often
forgotten that neurons optimized cellular signaling modes that existed long
before the CNS appeared during evolution, and were used by somatic cellular
networks to orchestrate physiology, embryonic development, and behavior. Many
of the key dynamics that enable information processing can, in fact, be
implemented by different biological hardware. This is widely exploited by
organisms throughout the tree of life. Here, we review data on memory,
learning, and other aspects of cognition in a range of models, including single
celled organisms, plants, and tissues in animal bodies. We discuss current knowledge
of the molecular mechanisms at work in these systems, and suggest several
hypotheses for future investigation. The study of cognitive processes
implemented in aneural contexts is a fascinating, highly interdisciplinary
topic that has many implications for evolution, cell biology, regenerative
medicine, computer science, and synthetic
bioengineering.","container-title":"Frontiers in
Psychology","DOI":"10.3389/fpsyg.2016.00902","ISSN":"1664-1078","journalAbbreviation":"Front
Psychol","language":"eng","note":"PMID:
27445884\nPMCID:
PMC4914563","page":"902","source":"PubMed","title":"On
Having No Head: Cognition throughout Biological
Systems","title-short":"On Having No
Head","volume":"7","author":[{"family":"Baluška","given":"František"},{"family":"Levin","given":"Michael"}],"issued":{"date-parts":[["2016"]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}
<span style='mso-element:field-separator'></span></span><![endif]--><sup><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;line-height:150%;font-family:
Times">1,2,44</span></sup><!--[if supportFields]><span lang=EN-GB
style='font-size:10.0pt;line-height:150%;font-family:Times;mso-ansi-language:
EN-GB'><span style='mso-element:field-end'></span></span><![endif]--><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB">.</span><span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB"></span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><br>
</p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><font size="-1">Waiting
for your comments and opinions,</font></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><font size="-1">Best
regards to all!</font></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
text-indent:35.4pt;line-height:150%"><font size="-1">Youri<br>
<span
style="font-size:10.0pt;line-height:150%;font-family:Times;
mso-ansi-language:EN-GB" lang="EN-GB"><o:p></o:p></span></font></p>
<font size="-1">
</font>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"><span
style="font-size:9.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB"><br>
</span><span style="font-size:9.0pt;line-height:150%;
font-family:Times;mso-ansi-language:EN-GB" lang="EN-GB"><br>
</span></p>
<p class="MsoNormal"
style="text-align:justify;text-justify:inter-ideograph;
line-height:150%"></p>
<p class="MsoNormal"><!--[if supportFields]><span style='font-size:8.0pt;
mso-bidi-font-family:"Times New Roman"'><span style='mso-element:field-begin'></span><span
style="mso-spacerun:yes"> </span>ADDIN ZOTERO_BIBL
{"uncited":[],"omitted":[],"custom":[]}
CSL_BIBLIOGRAPHY <span style='mso-element:field-separator'></span></span><![endif]--><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;font-family:Times">1.
Marijuán, P. C., Navarro, J. & del
Moral, R. How the living is in the world: An inquiry into
the informational
choreographies of life. <i>Prog Biophys Mol Biol</i> <b>119</b>,
469–480
(2015).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">2. Timsit, Y.
& Grégoire, S.-P. Towards the Idea of Molecular Brains.
<i>International
Journal of Molecular Sciences</i> <b>22</b>, 11868
(2021).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">3. Bray, D.
Protein molecules as computational elements in living cells.
<i>Nature</i> <b>376</b>,
307–312 (1995).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">4. Baluška, F.,
Miller, W. B. & Reber, A. S. Biomolecular Basis of
Cellular Consciousness
via Subcellular Nanobrains. <i>International Journal of
Molecular Sciences</i> <b>22</b>,
2545 (2021).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">5. Belousoff,
M. J. <i>et al.</i> Ancient machinery embedded in the
contemporary ribosome. <i>Biochem.
Soc. Trans.</i> <b>38</b>, 422–427 (2010).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">6. Fox, G. E.
Origin and evolution of the ribosome. <i>Cold Spring Harb
Perspect Biol</i> <b>2</b>,
a003483 (2010).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">7. Opron, K.
& Burton, Z. F. Ribosome Structure, Function, and Early
Evolution. <i>Int J
Mol Sci</i> <b>20</b>, (2018).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">8. Melnikov, S.
<i>et al.</i> One core, two shells: bacterial and eukaryotic
ribosomes. <i>Nat.
Struct. Mol. Biol.</i> <b>19</b>, 560–567 (2012).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">9. Lecompte,
O., Ripp, R., Thierry, J.-C., Moras, D. & Poch, O.
Comparative analysis of
ribosomal proteins in complete genomes: an example of
reductive evolution at
the domain scale. <i>Nucleic Acids Res.</i> <b>30</b>,
5382–5390 (2002).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">10. Petrov, A.
S. <i>et al.</i> History of the ribosome and the origin of
translation. <i>Proc.
Natl. Acad. Sci. U.S.A.</i> <b>112</b>, 15396–15401
(2015).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">11. Grosjean, H.
& Westhof, E. An integrated, structure- and energy-based
view of the
genetic code. <i>Nucleic Acids Res.</i> <b>44</b>,
8020–8040 (2016).<o:p></o:p></span></p>
<p class="MsoNormal"><span
style="font-size:10.0pt;mso-bidi-font-size:12.0pt;
font-family:Times">12. Root-Bernstein,
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