Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock
During heat shock and other proteotoxic stresses, cells regulate multiple steps in gene expression in order to globally repress protein synthesis and selectively upregulate stress response proteins. Splicing of several mRNAs is known to be inhibited during heat stress, often meditated by SRp38, but...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96258 https://orcid.org/0000-0003-1307-882X https://orcid.org/0000-0002-7589-1798 |
| _version_ | 1826191942331924480 |
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| author | Shalgi, Reut Hurt, Jessica A. Lindquist, Susan Burge, Christopher B |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Shalgi, Reut Hurt, Jessica A. Lindquist, Susan Burge, Christopher B |
| author_sort | Shalgi, Reut |
| collection | MIT |
| description | During heat shock and other proteotoxic stresses, cells regulate multiple steps in gene expression in order to globally repress protein synthesis and selectively upregulate stress response proteins. Splicing of several mRNAs is known to be inhibited during heat stress, often meditated by SRp38, but the extent and specificity of this effect have remained unclear. Here, we examined splicing regulation genome-wide during heat shock in mouse fibroblasts. We observed widespread retention of introns in transcripts from ~1,700 genes, which were enriched for tRNA synthetase, nuclear pore, and spliceosome functions. Transcripts with retained introns were largely nuclear and untranslated. However, a group of 580+ genes biased for oxidation reduction and protein folding functions continued to be efficiently spliced. Interestingly, these unaffected transcripts are mostly cotranscriptionally spliced under both normal and stress conditions, whereas splicing-inhibited transcripts are mostly spliced posttranscriptionally. Altogether, our data demonstrate widespread repression of splicing in the mammalian heat stress response, disproportionately affecting posttranscriptionally spliced genes. |
| first_indexed | 2024-09-23T09:03:44Z |
| format | Article |
| id | mit-1721.1/96258 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:03:44Z |
| publishDate | 2015 |
| publisher | Elsevier |
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| spelling | mit-1721.1/962582022-09-26T10:11:15Z Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock Shalgi, Reut Hurt, Jessica A. Lindquist, Susan Burge, Christopher B Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Shalgi, Reut Hurt, Jessica A. Lindquist, Susan Burge, Christopher B. During heat shock and other proteotoxic stresses, cells regulate multiple steps in gene expression in order to globally repress protein synthesis and selectively upregulate stress response proteins. Splicing of several mRNAs is known to be inhibited during heat stress, often meditated by SRp38, but the extent and specificity of this effect have remained unclear. Here, we examined splicing regulation genome-wide during heat shock in mouse fibroblasts. We observed widespread retention of introns in transcripts from ~1,700 genes, which were enriched for tRNA synthetase, nuclear pore, and spliceosome functions. Transcripts with retained introns were largely nuclear and untranslated. However, a group of 580+ genes biased for oxidation reduction and protein folding functions continued to be efficiently spliced. Interestingly, these unaffected transcripts are mostly cotranscriptionally spliced under both normal and stress conditions, whereas splicing-inhibited transcripts are mostly spliced posttranscriptionally. Altogether, our data demonstrate widespread repression of splicing in the mammalian heat stress response, disproportionately affecting posttranscriptionally spliced genes. Weizmann Institute of Science (Postdoctoral Award for Advancing Women in Science) European Molecular Biology Organization (Long-term Fellowship) Machiah Foundation National Science Foundation (U.S.) (Grant 0821391) National Institutes of Health (U.S.) 2015-03-30T18:21:10Z 2015-03-30T18:21:10Z 2014-05 2014-03 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/96258 Shalgi, Reut, Jessica A. Hurt, Susan Lindquist, and Christopher B. Burge. “Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome Following Heat Shock.” Cell Reports 7, no. 5 (June 2014): 1362–1370. https://orcid.org/0000-0003-1307-882X https://orcid.org/0000-0002-7589-1798 en_US http://dx.doi.org/10.1016/j.celrep.2014.04.044 Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Elsevier Elsevier Open Access |
| spellingShingle | Shalgi, Reut Hurt, Jessica A. Lindquist, Susan Burge, Christopher B Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock |
| title | Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock |
| title_full | Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock |
| title_fullStr | Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock |
| title_full_unstemmed | Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock |
| title_short | Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock |
| title_sort | widespread inhibition of posttranscriptional splicing shapes the cellular transcriptome following heat shock |
| url | http://hdl.handle.net/1721.1/96258 https://orcid.org/0000-0003-1307-882X https://orcid.org/0000-0002-7589-1798 |
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