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Circadian control of stress granules by oscillating EIF2α

Stress granule formation is important for stress response in normal cells and could lead to chemotherapy resistance in cancer cells. Aberrant stress granule dynamics are also known to disrupt proteostasis, affect RNA metabolism, and contribute to neuronal cell death. Meanwhile, circadian abnormality...

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Autores principales: Wang, Ruiqi, Jiang, Xin, Bao, Puhua, Qin, Meiling, Xu, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399301/
https://www.ncbi.nlm.nih.gov/pubmed/30833545
http://dx.doi.org/10.1038/s41419-019-1471-y
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author Wang, Ruiqi
Jiang, Xin
Bao, Puhua
Qin, Meiling
Xu, Jin
author_facet Wang, Ruiqi
Jiang, Xin
Bao, Puhua
Qin, Meiling
Xu, Jin
author_sort Wang, Ruiqi
collection PubMed
description Stress granule formation is important for stress response in normal cells and could lead to chemotherapy resistance in cancer cells. Aberrant stress granule dynamics are also known to disrupt proteostasis, affect RNA metabolism, and contribute to neuronal cell death. Meanwhile, circadian abnormality is an aging-related risk factor for cancer and neurodegeneration. Whether stress granule dynamics are circadian regulated is entirely unknown. Here we show that the formation of stress granules varied by zeitgeber time in mouse liver. Moreover, altering circadian regulation by silencing the core circadian gene Bmal1 in a cell line expressing an endogenous GFP-tagged G3BP1 significantly increased stress granule dynamics, while the overexpression of Bmal1 decreased them. Surprisingly, increased stress granule dynamics and formation by transient decrease of BMAL1 coincided with increased resistance to stress-induced cell death. The circadian regulation of stress granules was mediated by oscillating eIF2α expression. At zeitgeber time when BMAL1 and eIF2α were at nadir, reduction of unphosphorylated eIF2α could significantly alter the ratio of phosphorylated/total eIF2α and quickly lead to increased formation of stress granules. Therefore, diurnal oscillating eIF2α connects the circadian cue to a cellular stress response mechanism that is vital for both neurodegeneration and cancer.
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spelling pubmed-63993012019-03-05 Circadian control of stress granules by oscillating EIF2α Wang, Ruiqi Jiang, Xin Bao, Puhua Qin, Meiling Xu, Jin Cell Death Dis Article Stress granule formation is important for stress response in normal cells and could lead to chemotherapy resistance in cancer cells. Aberrant stress granule dynamics are also known to disrupt proteostasis, affect RNA metabolism, and contribute to neuronal cell death. Meanwhile, circadian abnormality is an aging-related risk factor for cancer and neurodegeneration. Whether stress granule dynamics are circadian regulated is entirely unknown. Here we show that the formation of stress granules varied by zeitgeber time in mouse liver. Moreover, altering circadian regulation by silencing the core circadian gene Bmal1 in a cell line expressing an endogenous GFP-tagged G3BP1 significantly increased stress granule dynamics, while the overexpression of Bmal1 decreased them. Surprisingly, increased stress granule dynamics and formation by transient decrease of BMAL1 coincided with increased resistance to stress-induced cell death. The circadian regulation of stress granules was mediated by oscillating eIF2α expression. At zeitgeber time when BMAL1 and eIF2α were at nadir, reduction of unphosphorylated eIF2α could significantly alter the ratio of phosphorylated/total eIF2α and quickly lead to increased formation of stress granules. Therefore, diurnal oscillating eIF2α connects the circadian cue to a cellular stress response mechanism that is vital for both neurodegeneration and cancer. Nature Publishing Group UK 2019-03-04 /pmc/articles/PMC6399301/ /pubmed/30833545 http://dx.doi.org/10.1038/s41419-019-1471-y Text en © The Author(s) 2019 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
Wang, Ruiqi
Jiang, Xin
Bao, Puhua
Qin, Meiling
Xu, Jin
Circadian control of stress granules by oscillating EIF2α
title Circadian control of stress granules by oscillating EIF2α
title_full Circadian control of stress granules by oscillating EIF2α
title_fullStr Circadian control of stress granules by oscillating EIF2α
title_full_unstemmed Circadian control of stress granules by oscillating EIF2α
title_short Circadian control of stress granules by oscillating EIF2α
title_sort circadian control of stress granules by oscillating eif2α
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399301/
https://www.ncbi.nlm.nih.gov/pubmed/30833545
http://dx.doi.org/10.1038/s41419-019-1471-y
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