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Translation elongation can control translation initiation on eukaryotic mRNAs

Chu, Dominique, Kazana, Eleanna, Bellanger, Noémie, Singh, Tarun, Tuite, Mick F., von der Haar, Tobias (2014) Translation elongation can control translation initiation on eukaryotic mRNAs. EMBO Journal, 33 (1). pp. 21-34. ISSN 0261-4189. (doi:10.1002/embj.201385651)

Abstract

Synonymous codons encode the same amino acid, but differ in other biophysical properties. The evolutionary selection of codons whose properties are optimal for a cell generates the phenomenon of codon bias. Although recent studies have shown strong effects of codon usage changes on protein expression levels and cellular physiology, no translational control mechanism is known that links codon usage to protein expression levels. Here, we demonstrate a novel translational control mechanism that responds to the speed of ribosome movement immediately after the start codon. High initiation rates are only possible if start codons are liberated sufficiently fast, thus accounting for the observation that fast codons are overrepresented in highly expressed proteins. In contrast, slow codons lead to slow liberation of the start codon by initiating ribosomes, thereby interfering with efficient translation initiation. Codon usage thus evolved as a means to optimise translation on individual mRNAs, as well as global optimisation of ribosome availability.

Item Type: Article
DOI/Identification number: 10.1002/embj.201385651
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QR Microbiology
Divisions: Faculties > Sciences > School of Computing > Applied and Interdisciplinary Informatics Group
Faculties > Sciences > School of Computing > Computational Intelligence Group
Depositing User: Dominique Chu
Date Deposited: 15 Oct 2015 08:00 UTC
Last Modified: 06 Mar 2020 04:07 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/51030 (The current URI for this page, for reference purposes)
Chu, Dominique: https://orcid.org/0000-0002-3706-2905
von der Haar, Tobias: https://orcid.org/0000-0002-6031-9254
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