Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock

Citations Over TimeTop 10% of 2014 papers

Abstract

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.

Related Papers

• → Aberrant expression and regulatory network of splicing factor-SRSF3 in tumors(2020)35 cited
• → The eukaryotic translation initiation factor eIF4E reprograms alternative splicing(2023)25 cited
• → XE7: A novel splicing factor that interacts with ASF/SF2 and ZNF265(2006)23 cited
• → SAP30BP interacts with RBM17/SPF45 to promote splicing in a subset of human short introns(2022)
• → Supplementary Figures S1-8 from METTL3-Mediated m<sup>6</sup>A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL(2023)