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Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code

Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were describ...

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Autores principales: Rozov, Alexey, Demeshkina, Natalia, Khusainov, Iskander, Westhof, Eric, Yusupov, Marat, Yusupova, Gulnara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736104/
https://www.ncbi.nlm.nih.gov/pubmed/26791911
http://dx.doi.org/10.1038/ncomms10457
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author Rozov, Alexey
Demeshkina, Natalia
Khusainov, Iskander
Westhof, Eric
Yusupov, Marat
Yusupova, Gulnara
author_facet Rozov, Alexey
Demeshkina, Natalia
Khusainov, Iskander
Westhof, Eric
Yusupov, Marat
Yusupova, Gulnara
author_sort Rozov, Alexey
collection PubMed
description Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNA(Lys)(UUU) with hypermodified 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine–pyrimidine mismatches. We show that mnm(5)s(2)U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism.
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spelling pubmed-47361042016-03-04 Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code Rozov, Alexey Demeshkina, Natalia Khusainov, Iskander Westhof, Eric Yusupov, Marat Yusupova, Gulnara Nat Commun Article Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNA(Lys)(UUU) with hypermodified 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine–pyrimidine mismatches. We show that mnm(5)s(2)U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism. Nature Publishing Group 2016-01-21 /pmc/articles/PMC4736104/ /pubmed/26791911 http://dx.doi.org/10.1038/ncomms10457 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Rozov, Alexey
Demeshkina, Natalia
Khusainov, Iskander
Westhof, Eric
Yusupov, Marat
Yusupova, Gulnara
Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code
title Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code
title_full Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code
title_fullStr Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code
title_full_unstemmed Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code
title_short Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code
title_sort novel base-pairing interactions at the trna wobble position crucial for accurate reading of the genetic code
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736104/
https://www.ncbi.nlm.nih.gov/pubmed/26791911
http://dx.doi.org/10.1038/ncomms10457
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