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Codon optimality controls differential mRNA translation during amino acid starvation

It is common wisdom that codon usage bias has evolved in the selection for efficient translation, in which highly expressed genes are encoded predominantly by optimal codons. However, a growing body of evidence suggests regulatory roles for non-optimal codons in translation dynamics. Here we report...

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Autores principales: Saikia, Mridusmita, Wang, Xiaoyun, Mao, Yuanhui, Wan, Ji, Pan, Tao, Qian, Shu-Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066624/
https://www.ncbi.nlm.nih.gov/pubmed/27613579
http://dx.doi.org/10.1261/rna.058180.116
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author Saikia, Mridusmita
Wang, Xiaoyun
Mao, Yuanhui
Wan, Ji
Pan, Tao
Qian, Shu-Bing
author_facet Saikia, Mridusmita
Wang, Xiaoyun
Mao, Yuanhui
Wan, Ji
Pan, Tao
Qian, Shu-Bing
author_sort Saikia, Mridusmita
collection PubMed
description It is common wisdom that codon usage bias has evolved in the selection for efficient translation, in which highly expressed genes are encoded predominantly by optimal codons. However, a growing body of evidence suggests regulatory roles for non-optimal codons in translation dynamics. Here we report that in mammalian cells, non-optimal codons play a critical role in promoting selective mRNA translation during amino acid starvation. During starvation, in contrast to genes encoding ribosomal proteins whose translation is highly sensitive to amino acid deprivation, translation of genes involved in the cellular protein degradation pathways remains unaffected. We found that these two gene groups bear different codon composition, with non-optimal codons being highly enriched in genes encoding the ubiquitin–proteasome system. Supporting the selective tRNA charging model originally proposed in Escherichia coli, we demonstrated that tRNA isoacceptors decoding rare codons are maintained in translating ribosomes under amino acid starvation. Finally, using luciferase reporters fused with endogenous gene-derived sequences, we show that codon optimality contributes to differential mRNA translation in response to amino acid starvation. These results highlight the physiological significance of codon usage bias in cellular adaptation to stress.
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spelling pubmed-50666242017-11-01 Codon optimality controls differential mRNA translation during amino acid starvation Saikia, Mridusmita Wang, Xiaoyun Mao, Yuanhui Wan, Ji Pan, Tao Qian, Shu-Bing RNA Article It is common wisdom that codon usage bias has evolved in the selection for efficient translation, in which highly expressed genes are encoded predominantly by optimal codons. However, a growing body of evidence suggests regulatory roles for non-optimal codons in translation dynamics. Here we report that in mammalian cells, non-optimal codons play a critical role in promoting selective mRNA translation during amino acid starvation. During starvation, in contrast to genes encoding ribosomal proteins whose translation is highly sensitive to amino acid deprivation, translation of genes involved in the cellular protein degradation pathways remains unaffected. We found that these two gene groups bear different codon composition, with non-optimal codons being highly enriched in genes encoding the ubiquitin–proteasome system. Supporting the selective tRNA charging model originally proposed in Escherichia coli, we demonstrated that tRNA isoacceptors decoding rare codons are maintained in translating ribosomes under amino acid starvation. Finally, using luciferase reporters fused with endogenous gene-derived sequences, we show that codon optimality contributes to differential mRNA translation in response to amino acid starvation. These results highlight the physiological significance of codon usage bias in cellular adaptation to stress. Cold Spring Harbor Laboratory Press 2016-11 /pmc/articles/PMC5066624/ /pubmed/27613579 http://dx.doi.org/10.1261/rna.058180.116 Text en © 2016 Saikia et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Article
Saikia, Mridusmita
Wang, Xiaoyun
Mao, Yuanhui
Wan, Ji
Pan, Tao
Qian, Shu-Bing
Codon optimality controls differential mRNA translation during amino acid starvation
title Codon optimality controls differential mRNA translation during amino acid starvation
title_full Codon optimality controls differential mRNA translation during amino acid starvation
title_fullStr Codon optimality controls differential mRNA translation during amino acid starvation
title_full_unstemmed Codon optimality controls differential mRNA translation during amino acid starvation
title_short Codon optimality controls differential mRNA translation during amino acid starvation
title_sort codon optimality controls differential mrna translation during amino acid starvation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066624/
https://www.ncbi.nlm.nih.gov/pubmed/27613579
http://dx.doi.org/10.1261/rna.058180.116
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