The Transcriptional Response to Oxidative Stress is Independent of Stress-Granule Formation.
Title | The Transcriptional Response to Oxidative Stress is Independent of Stress-Granule Formation. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Singh A, Kandi AReddy, Jayaprakashappa D, Thuery G, Purohit DJ, Huelsmeier J, Singh R, Pothapragada SShruti, Ramaswami M, Bakthavachalu B |
Journal | Mol Biol Cell |
Pagination | mbcE21080418 |
Date Published | 2022 Jan 05 |
ISSN | 1939-4586 |
Abstract | Cells respond to stress with translational arrest, robust transcriptional changes, and transcription-independent formation of mRNP assemblies termed stress granules (SGs). Despite considerable interest in the role of SGs in oxidative, unfolded-protein and viral stress responses, whether and how SGs contribute to stress-induced transcription has not been rigorously examined. To address this, we characterized transcriptional changes in S2 cells induced by acute oxidative-stress and assessed how these were altered under conditions that disrupted SG assembly. Oxidative stress for 3-hours predominantly resulted in induction or upregulation of stress-responsive mRNAs whose levels peaked during recovery after stress cessation. The stress-transcriptome is enriched in mRNAs coding for chaperones, including HSP70s, small heat shock proteins, glutathione transferases, and several non-coding RNAs. Oxidative stress also induced cytoplasmic SGs that disassembled 3-hours after stress cessation. As expected, RNAi-mediated knockdown of the conserved G3BP1/Rasputin protein inhibited SG assembly. However, this disruption had no significant effect on the stress-induced transcriptional response or stress-induced translational arrest. Thus, SG assembly and stress-induced gene expression alterations appear to be driven by distinctive signaling processes. We suggest that while SG assembly represents a fast, transient mechanism, the transcriptional response enables a slower, longer-lasting mechanism for adaptation to and recovery from cell stress. |
DOI | 10.1091/mbc.E21-08-0418 |
Alternate Journal | Mol Biol Cell |
PubMed ID | 34985933 |