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Translation elongation can control translation initiation on eukaryotic mRNA s
Author(s) -
Chu Dominique,
Kazana Eleanna,
Bellanger Noémie,
Singh Tarun,
Tuite Mick F,
Haar Tobias
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201385651
Subject(s) - biology , translation (biology) , codon usage bias , ribosome , start codon , genetics , translational regulation , synonymous substitution , eukaryotic translation , protein biosynthesis , stop codon , ribosome profiling , transfer rna , messenger rna , computational biology , amino acid , gene , rna , genome
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 mRNA s, as well as global optimisation of ribosome availability.