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      Origins of tmRNA: the missing link in the birth of protein synthesis?

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      1 , 1 , 2 , *
      Nucleic Acids Research
      Oxford University Press

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          Abstract

          The RNA world hypothesis refers to the early period on earth in which RNA was central in assuring both genetic continuity and catalysis. The end of this era coincided with the development of the genetic code and protein synthesis, symbolized by the apparition of the first non-random messenger RNA (mRNA). Modern transfer-messenger RNA (tmRNA) is a unique hybrid molecule which has the properties of both mRNA and transfer RNA (tRNA). It acts as a key molecule during trans-translation, a major quality control pathway of modern bacterial protein synthesis. tmRNA shares many common characteristics with ancestral RNA. Here, we present a model in which proto-tmRNAs were the first molecules on earth to support non-random protein synthesis, explaining the emergence of early genetic code. In this way, proto-tmRNA could be the missing link between the first mRNA and tRNA molecules and modern ribosome-mediated protein synthesis.

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          Most cited references73

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          The origin of the genetic code.

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            The structural basis of ribosome activity in peptide bond synthesis.

            Using the atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with two substrate analogs, we establish that the ribosome is a ribozyme and address the catalytic properties of its all-RNA active site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond synthesis appears to resemble the reverse of the acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia coli) playing the same general base role as histidine-57 in chymotrypsin. The unusual pK(a) (where K(a) is the acid dissociation constant) required for A2486 to perform this function may derive in part from its hydrogen bonding to G2482 (G2447 in E. coli), which also interacts with a buried phosphate that could stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is largely formed by RNA but has significant contributions from proteins L4, L22, and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and L31e.
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              A production of amino acids under possible primitive earth conditions.

              S Miller (1953)
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                30 September 2016
                02 August 2016
                02 August 2016
                : 44
                : 17
                : 8041-8051
                Affiliations
                [1 ]Université de Rennes 1, CNRS UMR 6290 IGDR, Translation and Folding Team, 35042 Rennes cedex, France
                [2 ]Institut Universitaire de France
                Author notes
                [* ]To whom correspondence should be addressed. Tel: +33 2 23 23 45 07; Email: reynald.gillet@ 123456univ-rennes1.fr
                Article
                10.1093/nar/gkw693
                5041485
                27484476
                4b1b557f-a292-4aeb-9cce-9f8f80bf2d67
                © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 26 July 2016
                : 22 July 2016
                : 09 June 2016
                Page count
                Pages: 11
                Categories
                Survey and Summary
                Custom metadata
                30 September 2016

                Genetics
                Genetics

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