A potential role for RNA aminoacylation prior to its role in peptide synthesis.

Autor:	Radakovic A; HHMI, Department of Chemistry, The University of Chicago, Chicago, IL 60637.; Department of Genetics, Harvard Medical School, Boston, MA 02115., Lewicka A; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637., Todisco M; HHMI, Department of Chemistry, The University of Chicago, Chicago, IL 60637., Aitken HRM; HHMI, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114.; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138., Weiss Z; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138., Kim S; HHMI, Department of Chemistry, The University of Chicago, Chicago, IL 60637., Bannan A; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138., Piccirilli JA; HHMI, Department of Chemistry, The University of Chicago, Chicago, IL 60637.; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637., Szostak JW; HHMI, Department of Chemistry, The University of Chicago, Chicago, IL 60637.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Aug 27; Vol. 121 (35), pp. e2410206121. Date of Electronic Publication: 2024 Aug 23.
DOI:	10.1073/pnas.2410206121
Abstrakt:	Coded ribosomal peptide synthesis could not have evolved unless its sequence and amino acid-specific aminoacylated tRNA substrates already existed. We therefore wondered whether aminoacylated RNAs might have served some primordial function prior to their role in protein synthesis. Here, we show that specific RNA sequences can be nonenzymatically aminoacylated and ligated to produce amino acid-bridged stem-loop RNAs. We used deep sequencing to identify RNAs that undergo highly efficient glycine aminoacylation followed by loop-closing ligation. The crystal structure of one such glycine-bridged RNA hairpin reveals a compact internally stabilized structure with the same eponymous T-loop architecture that is found in many noncoding RNAs, including the modern tRNA. We demonstrate that the T-loop-assisted amino acid bridging of RNA oligonucleotides enables the rapid template-free assembly of a chimeric version of an aminoacyl-RNA synthetase ribozyme. We suggest that the primordial assembly of amino acid-bridged chimeric ribozymes provides a direct and facile route for the covalent incorporation of amino acids into RNA. A greater functionality of covalently incorporated amino acids could contribute to enhanced ribozyme catalysis, providing a driving force for the evolution of sequence and amino acid-specific aminoacyl-RNA synthetase ribozymes in the RNA World. The synthesis of specifically aminoacylated RNAs, an unlikely prospect for nonenzymatic reactions but a likely one for ribozymes, could have set the stage for the subsequent evolution of coded protein synthesis. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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