title: Translation elongation can control translation initiation on eukaryotic mRNAs.
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.
authors.affiliation: School of Computing, University of Kent, Canterbury, UK.
authors.forename: Dominique
authors.initials: D
authors.lastname: Chu
authors.forename: Eleanna
authors.initials: E
authors.lastname: Kazana
authors.forename: Noémie
authors.initials: N
authors.lastname: Bellanger
authors.forename: Tarun
authors.initials: T
authors.lastname: Singh
authors.forename: Mick F
authors.initials: MF
authors.lastname: Tuite
authors.forename: Tobias
authors.initials: T
authors.lastname: von der Haar
mesh_terms: D018387:Codon, Initiator / Q000378:metabolism; D056890:Eukaryota; D005786:Gene Expression Regulation; D010441:Peptide Chain Elongation, Translational; D010442:Peptide Chain Initiation, Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
chemical_list: D018387:Codon, Initiator; D012333:RNA, Messenger