Recognition of 3' nucleotide context and stop codon readthrough are determined during mRNA translation elongation.

Autor:	Biziaev N; Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia., Sokolova E; Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia., Yanvarev DV; Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia., Toropygin IY; Orekhovich Research Institute of Biomedical Chemistry, Moscow, Russia., Shuvalov A; Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia., Egorova T; Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia; Department of Biochemistry, Faculty of Medicine and Biology, Pirogov Russian National Research Medical University, Moscow, Russia. Electronic address: tatvladegorova@gmail.com., Alkalaeva E; Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, The Russian Academy of Sciences, Moscow, Russia. Electronic address: alkalaeva@eimb.ru.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2022 Jul; Vol. 298 (7), pp. 102133. Date of Electronic Publication: 2022 Jun 11.
DOI:	10.1016/j.jbc.2022.102133
Abstrakt:	The nucleotide context surrounding stop codons significantly affects the efficiency of translation termination. In eukaryotes, various 3' contexts that are unfavorable for translation termination have been described; however, the exact molecular mechanism that mediates their effects remains unknown. In this study, we used a reconstituted mammalian translation system to examine the efficiency of stop codons in different contexts, including several previously described weak 3' stop codon contexts. We developed an approach to estimate the level of stop codon readthrough in the absence of eukaryotic release factors (eRFs). In this system, the stop codon is recognized by the suppressor or near-cognate tRNAs. We observed that in the absence of eRFs, readthrough occurs in a 3' nucleotide context-dependent manner, and the main factors determining readthrough efficiency were the type of stop codon and the sequence of the 3' nucleotides. Moreover, the efficiency of translation termination in weak 3' contexts was almost equal to that in the tested standard context. Therefore, the ability of eRFs to recognize stop codons and induce peptide release is not affected by mRNA context. We propose that ribosomes or other participants of the elongation cycle can independently recognize certain contexts and increase the readthrough of stop codons. Thus, the efficiency of translation termination is regulated by the 3' nucleotide context following the stop codon and depends on the concentrations of eRFs and suppressor/near-cognate tRNAs. Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest regarding the content of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu