Sequence complementarity at the ribosomal Peptidyl Transferase Centre implies self‐replicating origin

Agmon, Ilana

doi:10.1002/1873-3468.12781

Cited by 10 publications

(13 citation statements)

References 30 publications

(61 reference statements)

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“…Interestingly, copying the DPR monomers would have been particularly efficient, due to the sequence complementarity between nucleotides that constitute the two halves of the PTC cavity, observed in bacterial ribosomes. This complementarity implies that the sequence of each monomer could have acted as a template for the synthesis of its counterpart, eliminating the need for two replication steps for each copying event [20]. Variations introduced during the primitive replication phase would have launched Darwinian evolution at a molecular level, promoting selection for the fittest proto-ribosomes.…”

Section: Resultsmentioning

confidence: 99%

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Hypothesis: Spontaneous Advent of the Prebiotic Translation System via the Accumulation of L-Shaped RNA Elements

Agmon

2018

IJMS

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The feasibility of self-assembly of a translation system from prebiotic random RNA chains is a question that is central to the ability to conceive life emerging by natural processes. The spontaneous materialization of a translation system would have required the autonomous formation of proto-transfer RNA (tRNA) and proto-ribosome molecules that are indispensable for translating an RNA chain into a polypeptide. Currently, the vestiges of a non-coded proto-ribosome, which could have only catalyzed the formation of a peptide bond between random amino acids, is consensually localized in the region encircling the peptidyl transferase center of the ribosomal large subunit. The work presented here suggests, based on high resolution structures of ribosomes complexed with messenger RNA (mRNA) and tRNAs, that three types of L-shaped RNA building blocks derived from the modern ribosome, alongside with an L-shaped proto-tRNA, each composed of about 70-mer, could have randomly occurred in the prebiotic world and combined to form a simple translation system. The model of the initial coded proto-ribosome, which includes the active sites of both ribosomal subunits, together with a bridging element, incorporates less than 6% of the current prokaryotic rRNA, yet it integrates all of the ribosomal components that are vital for synthesizing the earliest coded polypeptides.

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Section: Resultsmentioning

confidence: 99%

“…3.) The sequence complementarity between nucleotides that constitute the two halves of the PTC cavity, observed in bacterial ribosomes, indicates an efficient replication mode for a dimeric proto-ribosome [20].…”

Section: Introductionmentioning

confidence: 99%

Hypothesis: Spontaneous Advent of the Prebiotic Translation System via the Accumulation of L-Shaped RNA Elements

Agmon

2018

IJMS

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“…However, GARD's chemical opportunism would allow compositional protocells to emerge that include catalytic and high-energy amphiphiles to generate a replicating protometabolism as described under the M-GARD title. In a very long series of evolutionary events, but in principle kinetically traceable, complexity would increases towards producing primitive versions of templating oligomers (proto RNA [ 243 ]), as well as protein-based protoenzymes and even proto-ribosomes [ 244 , 245 ]. This scenario would make it much less necessary for early life to depend on the less efficient ribozyme catalysis.…”

Section: Gard At Planetary Scalementioning

confidence: 99%

Systems protobiology: origin of life in lipid catalytic networks

Lancet

Zidovetzki

Markovitch

2018

J. R. Soc. Interface.

126

183

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Life is that which replicates and evolves, but there is no consensus on how life emerged. We advocate a systems protobiology view, whereby the first replicators were assemblies of spontaneously accreting, heterogeneous and mostly non-canonical amphiphiles. This view is substantiated by rigorous chemical kinetics simulations of the graded autocatalysis replication domain (GARD) model, based on the notion that the replication or reproduction of compositional information predated that of sequence information. GARD reveals the emergence of privileged non-equilibrium assemblies (composomes), which portray catalysis-based homeostatic (concentration-preserving) growth. Such a process, along with occasional assembly fission, embodies cell-like reproduction. GARD pre-RNA evolution is evidenced in the selection of different composomes within a sparse fitness landscape, in response to environmental chemical changes. These observations refute claims that GARD assemblies (or other mutually catalytic networks in the metabolism first scenario) cannot evolve. Composomes represent both a genotype and a selectable phenotype, anteceding present-day biology in which the two are mostly separated. Detailed GARD analyses show attractor-like transitions from random assemblies to self-organized composomes, with negative entropy change, thus establishing composomes as dissipative systems—hallmarks of life. We show a preliminary new version of our model, metabolic GARD (M-GARD), in which lipid covalent modifications are orchestrated by non-enzymatic lipid catalysts, themselves compositionally reproduced. M-GARD fills the gap of the lack of true metabolism in basic GARD, and is rewardingly supported by a published experimental instance of a lipid-based mutually catalytic network. Anticipating near-future far-reaching progress of molecular dynamics, M-GARD is slated to quantitatively depict elaborate protocells, with orchestrated reproduction of both lipid bilayer and lumenal content. Finally, a GARD analysis in a whole-planet context offers the potential for estimating the probability of life's emergence. The invigorated GARD scrutiny presented in this review enhances the validity of autocatalytic sets as a bona fide early evolution scenario and provides essential infrastructure for a paradigm shift towards a systems protobiology view of life's origin.

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“…The PTC is a universally conserved ribonucleotide chain that catalyzes the formation of peptide bonds during peptide chain synthesis and constitutes a highly selective drug target site within the ribosome 5. Indeed, being the heart of the gene translation machinery, most of the available antibacterial compounds that target the large (50S) ribosome subunit of bacteria act on the PTC 6,7…”

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confidence: 99%

Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis

et al. 2019

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Sequence complementarity at the ribosomal Peptidyl Transferase Centre implies self‐replicating origin

Cited by 10 publications

References 30 publications

Hypothesis: Spontaneous Advent of the Prebiotic Translation System via the Accumulation of L-Shaped RNA Elements

Hypothesis: Spontaneous Advent of the Prebiotic Translation System via the Accumulation of L-Shaped RNA Elements

Systems protobiology: origin of life in lipid catalytic networks

Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis

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