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Ribosome profiling reveals a functional role for autophagy in mRNA translational control

Autophagy promotes protein degradation, and therefore has been proposed to maintain amino acid pools to sustain protein synthesis during metabolic stress. To date, how autophagy influences the protein synthesis landscape in mammalian cells remains unclear. Here, we utilize ribosome profiling to deli...

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Autores principales: Goldsmith, Juliet, Marsh, Timothy, Asthana, Saurabh, Leidal, Andrew M., Suresh, Deepthisri, Olshen, Adam, Debnath, Jayanta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367890/
https://www.ncbi.nlm.nih.gov/pubmed/32681145
http://dx.doi.org/10.1038/s42003-020-1090-2
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author Goldsmith, Juliet
Marsh, Timothy
Asthana, Saurabh
Leidal, Andrew M.
Suresh, Deepthisri
Olshen, Adam
Debnath, Jayanta
author_facet Goldsmith, Juliet
Marsh, Timothy
Asthana, Saurabh
Leidal, Andrew M.
Suresh, Deepthisri
Olshen, Adam
Debnath, Jayanta
author_sort Goldsmith, Juliet
collection PubMed
description Autophagy promotes protein degradation, and therefore has been proposed to maintain amino acid pools to sustain protein synthesis during metabolic stress. To date, how autophagy influences the protein synthesis landscape in mammalian cells remains unclear. Here, we utilize ribosome profiling to delineate the effects of genetic ablation of the autophagy regulator, ATG12, on translational control. In mammalian cells, genetic loss of autophagy does not impact global rates of cap dependent translation, even under starvation conditions. Instead, autophagy supports the translation of a subset of mRNAs enriched for cell cycle control and DNA damage repair. In particular, we demonstrate that autophagy enables the translation of the DNA damage repair protein BRCA2, which is functionally required to attenuate DNA damage and promote cell survival in response to PARP inhibition. Overall, our findings illuminate that autophagy impacts protein translation and shapes the protein landscape.
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spelling pubmed-73678902020-07-21 Ribosome profiling reveals a functional role for autophagy in mRNA translational control Goldsmith, Juliet Marsh, Timothy Asthana, Saurabh Leidal, Andrew M. Suresh, Deepthisri Olshen, Adam Debnath, Jayanta Commun Biol Article Autophagy promotes protein degradation, and therefore has been proposed to maintain amino acid pools to sustain protein synthesis during metabolic stress. To date, how autophagy influences the protein synthesis landscape in mammalian cells remains unclear. Here, we utilize ribosome profiling to delineate the effects of genetic ablation of the autophagy regulator, ATG12, on translational control. In mammalian cells, genetic loss of autophagy does not impact global rates of cap dependent translation, even under starvation conditions. Instead, autophagy supports the translation of a subset of mRNAs enriched for cell cycle control and DNA damage repair. In particular, we demonstrate that autophagy enables the translation of the DNA damage repair protein BRCA2, which is functionally required to attenuate DNA damage and promote cell survival in response to PARP inhibition. Overall, our findings illuminate that autophagy impacts protein translation and shapes the protein landscape. Nature Publishing Group UK 2020-07-17 /pmc/articles/PMC7367890/ /pubmed/32681145 http://dx.doi.org/10.1038/s42003-020-1090-2 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
Goldsmith, Juliet
Marsh, Timothy
Asthana, Saurabh
Leidal, Andrew M.
Suresh, Deepthisri
Olshen, Adam
Debnath, Jayanta
Ribosome profiling reveals a functional role for autophagy in mRNA translational control
title Ribosome profiling reveals a functional role for autophagy in mRNA translational control
title_full Ribosome profiling reveals a functional role for autophagy in mRNA translational control
title_fullStr Ribosome profiling reveals a functional role for autophagy in mRNA translational control
title_full_unstemmed Ribosome profiling reveals a functional role for autophagy in mRNA translational control
title_short Ribosome profiling reveals a functional role for autophagy in mRNA translational control
title_sort ribosome profiling reveals a functional role for autophagy in mrna translational control
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367890/
https://www.ncbi.nlm.nih.gov/pubmed/32681145
http://dx.doi.org/10.1038/s42003-020-1090-2
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