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A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism
Protein expression evolves under greater evolutionary constraint than mRNA levels, and translation efficiency represents a primary determinant of protein levels during stimuli adaptation. This raises the question as to the translatome remodelers that titrate protein output from mRNA populations. Her...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260222/ https://www.ncbi.nlm.nih.gov/pubmed/32472050 http://dx.doi.org/10.1038/s41467-020-16504-1 |
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author | Ho, J. J. David Balukoff, Nathan C. Theodoridis, Phaedra R. Wang, Miling Krieger, Jonathan R. Schatz, Jonathan H. Lee, Stephen |
author_facet | Ho, J. J. David Balukoff, Nathan C. Theodoridis, Phaedra R. Wang, Miling Krieger, Jonathan R. Schatz, Jonathan H. Lee, Stephen |
author_sort | Ho, J. J. David |
collection | PubMed |
description | Protein expression evolves under greater evolutionary constraint than mRNA levels, and translation efficiency represents a primary determinant of protein levels during stimuli adaptation. This raises the question as to the translatome remodelers that titrate protein output from mRNA populations. Here, we uncover a network of RNA-binding proteins (RBPs) that enhances the translation efficiency of glycolytic proteins in cells responding to oxygen deprivation. A system-wide proteomic survey of translational engagement identifies a family of oxygen-regulated RBPs that functions as a switch of glycolytic intensity. Tandem mass tag-pulse SILAC (TMT-pSILAC) and RNA sequencing reveals that each RBP controls a unique but overlapping portfolio of hypoxic responsive proteins. These RBPs collaborate with the hypoxic protein synthesis apparatus, operating as a translation efficiency checkpoint that integrates upstream mRNA signals to activate anaerobic metabolism. This system allows anoxia-resistant animals and mammalian cells to initiate anaerobic glycolysis and survive hypoxia. We suggest that an oxygen-sensitive RBP cluster controls anaerobic metabolism to confer hypoxia tolerance. |
format | Online Article Text |
id | pubmed-7260222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72602222020-06-09 A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism Ho, J. J. David Balukoff, Nathan C. Theodoridis, Phaedra R. Wang, Miling Krieger, Jonathan R. Schatz, Jonathan H. Lee, Stephen Nat Commun Article Protein expression evolves under greater evolutionary constraint than mRNA levels, and translation efficiency represents a primary determinant of protein levels during stimuli adaptation. This raises the question as to the translatome remodelers that titrate protein output from mRNA populations. Here, we uncover a network of RNA-binding proteins (RBPs) that enhances the translation efficiency of glycolytic proteins in cells responding to oxygen deprivation. A system-wide proteomic survey of translational engagement identifies a family of oxygen-regulated RBPs that functions as a switch of glycolytic intensity. Tandem mass tag-pulse SILAC (TMT-pSILAC) and RNA sequencing reveals that each RBP controls a unique but overlapping portfolio of hypoxic responsive proteins. These RBPs collaborate with the hypoxic protein synthesis apparatus, operating as a translation efficiency checkpoint that integrates upstream mRNA signals to activate anaerobic metabolism. This system allows anoxia-resistant animals and mammalian cells to initiate anaerobic glycolysis and survive hypoxia. We suggest that an oxygen-sensitive RBP cluster controls anaerobic metabolism to confer hypoxia tolerance. Nature Publishing Group UK 2020-05-29 /pmc/articles/PMC7260222/ /pubmed/32472050 http://dx.doi.org/10.1038/s41467-020-16504-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ho, J. J. David Balukoff, Nathan C. Theodoridis, Phaedra R. Wang, Miling Krieger, Jonathan R. Schatz, Jonathan H. Lee, Stephen A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism |
title | A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism |
title_full | A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism |
title_fullStr | A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism |
title_full_unstemmed | A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism |
title_short | A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism |
title_sort | network of rna-binding proteins controls translation efficiency to activate anaerobic metabolism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260222/ https://www.ncbi.nlm.nih.gov/pubmed/32472050 http://dx.doi.org/10.1038/s41467-020-16504-1 |
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