Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells

Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis...

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Autores principales: Nüske, Elisabeth, Marini, Guendalina, Richter, Doris, Leng, Weihua, Bogdanova, Aliona, Franzmann, Titus M., Pigino, Gaia, Alberti, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358136/
https://www.ncbi.nlm.nih.gov/pubmed/32554487
http://dx.doi.org/10.1242/bio.046391
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author Nüske, Elisabeth
Marini, Guendalina
Richter, Doris
Leng, Weihua
Bogdanova, Aliona
Franzmann, Titus M.
Pigino, Gaia
Alberti, Simon
author_facet Nüske, Elisabeth
Marini, Guendalina
Richter, Doris
Leng, Weihua
Bogdanova, Aliona
Franzmann, Titus M.
Pigino, Gaia
Alberti, Simon
author_sort Nüske, Elisabeth
collection PubMed
description Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis are still unknown. Here, we report that the essential translation initiation factor eIF2B forms filaments in starved budding yeast cells. We demonstrate that filamentation is triggered by starvation-induced acidification of the cytosol, which is caused by an influx of protons from the extracellular environment. We show that filament assembly by eIF2B is necessary for rapid and efficient downregulation of translation. Importantly, this mechanism does not require the kinase Gcn2. Furthermore, analysis of site-specific variants suggests that eIF2B assembly results in enzymatically inactive filaments that promote stress survival and fast recovery of cells from starvation. We propose that translation regulation through filament assembly is an efficient mechanism that allows yeast cells to adapt to fluctuating environments.
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spelling pubmed-73581362020-07-14 Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells Nüske, Elisabeth Marini, Guendalina Richter, Doris Leng, Weihua Bogdanova, Aliona Franzmann, Titus M. Pigino, Gaia Alberti, Simon Biol Open Research Article Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis are still unknown. Here, we report that the essential translation initiation factor eIF2B forms filaments in starved budding yeast cells. We demonstrate that filamentation is triggered by starvation-induced acidification of the cytosol, which is caused by an influx of protons from the extracellular environment. We show that filament assembly by eIF2B is necessary for rapid and efficient downregulation of translation. Importantly, this mechanism does not require the kinase Gcn2. Furthermore, analysis of site-specific variants suggests that eIF2B assembly results in enzymatically inactive filaments that promote stress survival and fast recovery of cells from starvation. We propose that translation regulation through filament assembly is an efficient mechanism that allows yeast cells to adapt to fluctuating environments. The Company of Biologists Ltd 2020-07-08 /pmc/articles/PMC7358136/ /pubmed/32554487 http://dx.doi.org/10.1242/bio.046391 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Nüske, Elisabeth
Marini, Guendalina
Richter, Doris
Leng, Weihua
Bogdanova, Aliona
Franzmann, Titus M.
Pigino, Gaia
Alberti, Simon
Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
title Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
title_full Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
title_fullStr Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
title_full_unstemmed Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
title_short Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
title_sort filament formation by the translation factor eif2b regulates protein synthesis in starved cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358136/
https://www.ncbi.nlm.nih.gov/pubmed/32554487
http://dx.doi.org/10.1242/bio.046391
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