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Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States.

Published version
Peer-reviewed

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Authors

Rudolph, Konrad LM 
Schmitt, Bianca M 
Villar, Diego 
White, Robert J 
Marioni, John C 

Abstract

Whether codon usage fine-tunes mRNA translation in mammals remains controversial, with recent papers suggesting that production of proteins in specific Gene Ontological (GO) pathways can be regulated by actively modifying the codon and anticodon pools in different cellular conditions. In this work, we compared the sequence content of genes in specific GO categories with the exonic genome background. Although a substantial fraction of variability in codon usage could be explained by random sampling, almost half of GO sets showed more variability in codon usage than expected by chance. Nevertheless, by quantifying translational efficiency in healthy and cancerous tissues in human and mouse, we demonstrated that a given tRNA pool can equally well translate many different sets of mRNAs, irrespective of their cell-type specificity. This disconnect between variations in codon usage and the stability of translational efficiency is best explained by differences in GC content between gene sets. GC variation across the mammalian genome is most likely a result of the interplay between genome repair and gene duplication mechanisms, rather than selective pressures caused by codon-driven translational rates. Consequently, codon usage differences in mammalian transcriptomes are most easily explained by well-understood mutational biases acting on the underlying genome.

Description

Keywords

Animals, Anticodon, Base Composition, Codon, Gene Expression, Gene Ontology, Genomics, Humans, Mammals, Mice, Models, Genetic, Protein Biosynthesis, RNA, Messenger, RNA, Transfer, Selection, Genetic, Transcriptome

Journal Title

PLoS Genet

Conference Name

Journal ISSN

1553-7390
1553-7404

Volume Title

12

Publisher

Public Library of Science (PLoS)
Sponsorship
Cancer Research UK (C14303/A17197)
European Research Council (615584)
Cancer Research UK (22231)
Cancer Research UK (20412)
European Molecular Biology Laboratory