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Interstrand Aminoacyl Transfer in a tRNA Acceptor Stem-Overhang Mimic
[Image: see text] Protein-catalyzed aminoacylation of the 3′-overhang of tRNA by an aminoacyl-adenylate could not have taken place prior to the advent of genetically coded peptide synthesis, and yet the latter process has an absolute requirement for aminoacyl-tRNA. There must therefore have been an...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397310/ https://www.ncbi.nlm.nih.gov/pubmed/34283595 http://dx.doi.org/10.1021/jacs.1c05746 |
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author | Wu, Long-Fei Su, Meng Liu, Ziwei Bjork, Samuel J. Sutherland, John D. |
author_facet | Wu, Long-Fei Su, Meng Liu, Ziwei Bjork, Samuel J. Sutherland, John D. |
author_sort | Wu, Long-Fei |
collection | PubMed |
description | [Image: see text] Protein-catalyzed aminoacylation of the 3′-overhang of tRNA by an aminoacyl-adenylate could not have taken place prior to the advent of genetically coded peptide synthesis, and yet the latter process has an absolute requirement for aminoacyl-tRNA. There must therefore have been an earlier nonprotein-catalyzed means of generating aminoacyl-tRNA. Here, we demonstrate efficient interstrand aminoacyl transfer from an aminoacyl phosphate mixed anhydride at the 5′-terminus of a tRNA acceptor stem mimic to the 2′,3′-diol terminus of a short 3′-overhang. With certain five-base 3′-overhangs, the transfer of an alanyl residue is highly stereoselective with the l-enantiomer being favored to the extent of ∼10:1 over the d-enantiomer and is much more efficient than the transfer of a glycyl residue. N-Acyl-aminoacyl residues are similarly transferred from a mixed anhydride with the 5′-phosphate to the 2′,3′-diol but with a different dependence of efficiency and stereoselectivity on the 3′-overhang length and sequence. Given a prebiotically plausible and compatible synthesis of aminoacyl phosphate mixed anhydrides, these results suggest that RNA molecules with acceptor stem termini resembling modern tRNAs could have been spontaneously aminoacylated, in a stereoselective and chemoselective manner, at their 2′,3′-diol termini prior to the onset of protein-catalyzed aminoacylation. |
format | Online Article Text |
id | pubmed-8397310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-83973102021-08-31 Interstrand Aminoacyl Transfer in a tRNA Acceptor Stem-Overhang Mimic Wu, Long-Fei Su, Meng Liu, Ziwei Bjork, Samuel J. Sutherland, John D. J Am Chem Soc [Image: see text] Protein-catalyzed aminoacylation of the 3′-overhang of tRNA by an aminoacyl-adenylate could not have taken place prior to the advent of genetically coded peptide synthesis, and yet the latter process has an absolute requirement for aminoacyl-tRNA. There must therefore have been an earlier nonprotein-catalyzed means of generating aminoacyl-tRNA. Here, we demonstrate efficient interstrand aminoacyl transfer from an aminoacyl phosphate mixed anhydride at the 5′-terminus of a tRNA acceptor stem mimic to the 2′,3′-diol terminus of a short 3′-overhang. With certain five-base 3′-overhangs, the transfer of an alanyl residue is highly stereoselective with the l-enantiomer being favored to the extent of ∼10:1 over the d-enantiomer and is much more efficient than the transfer of a glycyl residue. N-Acyl-aminoacyl residues are similarly transferred from a mixed anhydride with the 5′-phosphate to the 2′,3′-diol but with a different dependence of efficiency and stereoselectivity on the 3′-overhang length and sequence. Given a prebiotically plausible and compatible synthesis of aminoacyl phosphate mixed anhydrides, these results suggest that RNA molecules with acceptor stem termini resembling modern tRNAs could have been spontaneously aminoacylated, in a stereoselective and chemoselective manner, at their 2′,3′-diol termini prior to the onset of protein-catalyzed aminoacylation. American Chemical Society 2021-07-20 2021-08-04 /pmc/articles/PMC8397310/ /pubmed/34283595 http://dx.doi.org/10.1021/jacs.1c05746 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Wu, Long-Fei Su, Meng Liu, Ziwei Bjork, Samuel J. Sutherland, John D. Interstrand Aminoacyl Transfer in a tRNA Acceptor Stem-Overhang Mimic |
title | Interstrand
Aminoacyl Transfer in a tRNA Acceptor
Stem-Overhang Mimic |
title_full | Interstrand
Aminoacyl Transfer in a tRNA Acceptor
Stem-Overhang Mimic |
title_fullStr | Interstrand
Aminoacyl Transfer in a tRNA Acceptor
Stem-Overhang Mimic |
title_full_unstemmed | Interstrand
Aminoacyl Transfer in a tRNA Acceptor
Stem-Overhang Mimic |
title_short | Interstrand
Aminoacyl Transfer in a tRNA Acceptor
Stem-Overhang Mimic |
title_sort | interstrand
aminoacyl transfer in a trna acceptor
stem-overhang mimic |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397310/ https://www.ncbi.nlm.nih.gov/pubmed/34283595 http://dx.doi.org/10.1021/jacs.1c05746 |
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