Transcriptome-wide mRNA condensation precedes stress granule formation and excludes stress-induced transcripts.
| العنوان: | Transcriptome-wide mRNA condensation precedes stress granule formation and excludes stress-induced transcripts. |
|---|---|
| المؤلفون: | Glauninger H; Graduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL, USA.; Interdisciplinary Scientist Training Program, The University of Chicago, Chicago, IL, USA., Bard JAM; Department of Biology, Texas A&M University, College Station, TX, USA., Wong Hickernell CJ; Department of Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA., Airoldi EM; Fox School of Business and Management, Temple University, Philadelphia, PA, USA., Li W; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY, USA., Singer RH; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY, USA.; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY, USA.; Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA., Paul S; Department of Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA., Fei J; Department of Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA.; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA., Sosnick TR; Department of Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA.; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA.; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA., Wallace EWJ; School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, UK., Drummond DA; Department of Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA.; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA.; Department of Medicine, Section of Genetic Medicine, The University of Chicago, Chicago, IL, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 May 02. Date of Electronic Publication: 2024 May 02. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Stress-induced condensation of mRNA and proteins into stress granules is conserved across eukaryotes, yet the function, formation mechanisms, and relation to well-studied conserved transcriptional responses remain largely unresolved. Stress-induced exposure of ribosome-free mRNA following translational shutoff is thought to cause condensation by allowing new multivalent RNA-dependent interactions, with RNA length and associated interaction capacity driving increased condensation. Here we show that, in striking contrast, virtually all mRNA species condense in response to multiple unrelated stresses in budding yeast, length plays a minor role, and instead, stress-induced transcripts are preferentially excluded from condensates, enabling their selective translation. Using both endogenous genes and reporter constructs, we show that translation initiation blockade, rather than resulting ribosome-free RNA, causes condensation. These translation initiation-inhibited condensates (TIICs) are biochemically detectable even when stress granules, defined as microscopically visible foci, are absent or blocked. TIICs occur in unstressed yeast cells, and, during stress, grow before the appearance of visible stress granules. Stress-induced transcripts are excluded from TIICs primarily due to the timing of their expression, rather than their sequence features. Together, our results reveal a simple system by which cells redirect translational activity to newly synthesized transcripts during stress, with broad implications for cellular regulation in changing conditions. |
| معلومات مُعتمدة: | K99 GM148788 United States GM NIGMS NIH HHS; R01 GM055694 United States GM NIGMS NIH HHS; R35 GM144278 United States GM NIGMS NIH HHS; F30 ES032665 United States ES NIEHS NIH HHS; United Kingdom WT_ Wellcome Trust; F31 ES033554 United States ES NIEHS NIH HHS |
| تواريخ الأحداث: | Date Created: 20240425 Latest Revision: 20240629 |
| رمز التحديث: | 20240629 |
| مُعرف محوري في PubMed: | PMC11042329 |
| DOI: | 10.1101/2024.04.15.589678 |
| PMID: | 38659805 |
| قاعدة البيانات: | MEDLINE |
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