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

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,...

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Main Authors:	Rudolph, Konrad L. M., Schmitt, Bianca M., Villar, Diego, White, Robert J., Marioni, John C., Kutter, Claudia, Odom, Duncan T.
Format:	Online
Language:	English
Published:	Public Library of Science 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864286/

id	pubmed-4864286
recordtype	oai_dc
spelling	pubmed-48642862016-05-18 Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States Rudolph, Konrad L. M. Schmitt, Bianca M. Villar, Diego White, Robert J. Marioni, John C. Kutter, Claudia Odom, Duncan T. Research Article 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. Public Library of Science 2016-05-11 /pmc/articles/PMC4864286/ /pubmed/27166679 http://dx.doi.org/10.1371/journal.pgen.1006024 Text en © 2016 Rudolph et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rudolph, Konrad L. M. Schmitt, Bianca M. Villar, Diego White, Robert J. Marioni, John C. Kutter, Claudia Odom, Duncan T.
spellingShingle	Rudolph, Konrad L. M. Schmitt, Bianca M. Villar, Diego White, Robert J. Marioni, John C. Kutter, Claudia Odom, Duncan T. Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States
author_facet	Rudolph, Konrad L. M. Schmitt, Bianca M. Villar, Diego White, Robert J. Marioni, John C. Kutter, Claudia Odom, Duncan T.
author_sort	Rudolph, Konrad L. M.
title	Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States
title_short	Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States
title_full	Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States
title_fullStr	Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States
title_full_unstemmed	Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States
title_sort	codon-driven translational efficiency is stable across diverse mammalian cell states
description	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.
publisher	Public Library of Science
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864286/
_version_	1613578272438747136

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

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