Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782460516624498688 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5066624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT saikiamridusmita codonoptimalitycontrolsdifferentialmrnatranslationduringaminoacidstarvation AT wangxiaoyun codonoptimalitycontrolsdifferentialmrnatranslationduringaminoacidstarvation AT maoyuanhui codonoptimalitycontrolsdifferentialmrnatranslationduringaminoacidstarvation AT wanji codonoptimalitycontrolsdifferentialmrnatranslationduringaminoacidstarvation AT pantao codonoptimalitycontrolsdifferentialmrnatranslationduringaminoacidstarvation AT qianshubing codonoptimalitycontrolsdifferentialmrnatranslationduringaminoacidstarvation |