Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.

Specific interaction between the start codon, 5'-AUG-3', and the anticodon, 5'-CAU-3', ensures accurate initiation of translation. Recent studies show that several near-cognate start codons (e.g. GUG and CUG) can play a role in initiating translation in eukaryotes. However, the m...

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Autores principales:	Takeru Kameda, Katsura Asano, Yuichi Togashi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3fd7abd4013542a98b509ad18fb2da86
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spelling	oai:doaj.org-article:3fd7abd4013542a98b509ad18fb2da862021-11-25T05:40:37ZFree energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.1553-734X1553-735810.1371/journal.pcbi.1009068https://doaj.org/article/3fd7abd4013542a98b509ad18fb2da862021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009068https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Specific interaction between the start codon, 5'-AUG-3', and the anticodon, 5'-CAU-3', ensures accurate initiation of translation. Recent studies show that several near-cognate start codons (e.g. GUG and CUG) can play a role in initiating translation in eukaryotes. However, the mechanism allowing initiation through mismatched base-pairs at the ribosomal decoding site is still unclear at an atomic level. In this work, we propose an extended simulation-based method to evaluate free energy profiles, through computing the distance between each base-pair of the triplet interactions involved in recognition of start codons in eukaryotic translation pre-initiation complex. Our method provides not only the free energy penalty for mismatched start codons relative to the AUG start codon, but also the preferred pathways of transitions between bound and unbound states, which has not been described by previous studies. To verify the method, the binding dynamics of cognate (AUG) and near-cognate start codons (CUG and GUG) were simulated. Evaluated free energy profiles agree with experimentally observed changes in initiation frequencies from respective codons. This work proposes for the first time how a G:U mismatch at the first position of codon (GUG)-anticodon base-pairs destabilizes the accommodation in the initiating eukaryotic ribosome and how initiation at a CUG codon is nearly as strong as, or sometimes stronger than, that at a GUG codon. Our method is expected to be applied to study the affinity changes for various mismatched base-pairs.Takeru KamedaKatsura AsanoYuichi TogashiPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 6, p e1009068 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Takeru Kameda Katsura Asano Yuichi Togashi Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.
description	Specific interaction between the start codon, 5'-AUG-3', and the anticodon, 5'-CAU-3', ensures accurate initiation of translation. Recent studies show that several near-cognate start codons (e.g. GUG and CUG) can play a role in initiating translation in eukaryotes. However, the mechanism allowing initiation through mismatched base-pairs at the ribosomal decoding site is still unclear at an atomic level. In this work, we propose an extended simulation-based method to evaluate free energy profiles, through computing the distance between each base-pair of the triplet interactions involved in recognition of start codons in eukaryotic translation pre-initiation complex. Our method provides not only the free energy penalty for mismatched start codons relative to the AUG start codon, but also the preferred pathways of transitions between bound and unbound states, which has not been described by previous studies. To verify the method, the binding dynamics of cognate (AUG) and near-cognate start codons (CUG and GUG) were simulated. Evaluated free energy profiles agree with experimentally observed changes in initiation frequencies from respective codons. This work proposes for the first time how a G:U mismatch at the first position of codon (GUG)-anticodon base-pairs destabilizes the accommodation in the initiating eukaryotic ribosome and how initiation at a CUG codon is nearly as strong as, or sometimes stronger than, that at a GUG codon. Our method is expected to be applied to study the affinity changes for various mismatched base-pairs.
format	article
author	Takeru Kameda Katsura Asano Yuichi Togashi
author_facet	Takeru Kameda Katsura Asano Yuichi Togashi
author_sort	Takeru Kameda
title	Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.
title_short	Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.
title_full	Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.
title_fullStr	Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.
title_full_unstemmed	Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.
title_sort	free energy landscape of rna binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3fd7abd4013542a98b509ad18fb2da86
work_keys_str_mv	AT takerukameda freeenergylandscapeofrnabindingdynamicsinstartcodonrecognitionbyeukaryoticribosomalpreinitiationcomplex AT katsuraasano freeenergylandscapeofrnabindingdynamicsinstartcodonrecognitionbyeukaryoticribosomalpreinitiationcomplex AT yuichitogashi freeenergylandscapeofrnabindingdynamicsinstartcodonrecognitionbyeukaryoticribosomalpreinitiationcomplex
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Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex.

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