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Heat shock induces premature transcript termination and reconfigures the human transcriptome
Simona Cugusi1, Richard Mitter2, Gavin P Kelly2
1Mechanisms of Transcription Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Molecular Cell
|February 3, 2022
Summary
Heat shock (HS) response rapidly induces HS genes but represses others by affecting RNA polymerase II (RNAPII) transcription. HS causes premature termination at intronic polyadenylation sites, creating novel short mRNAs.
Area of Science:
- Molecular Biology
- Gene Regulation
- Transcriptomics
Background:
- The heat shock (HS) response rapidly upregulates specific genes while generally repressing others.
- Previous studies suggested HS-induced repression involves inhibiting RNA polymerase II (RNAPII) pause release.
Purpose of the Study:
- To investigate the broader impact of HS on the transcription cycle beyond RNAPII pause release.
- To elucidate the mechanisms underlying HS-induced transcriptional repression and transcriptome reconfiguration.
Main Methods:
- Analysis of RNA polymerase II (RNAPII) dynamics during heat shock.
- Identification of premature transcript termination sites.
- Transcriptome-wide analysis of mRNA production and localization.
Main Results:
- HS affects multiple phases of the transcription cycle, not just RNAPII pause release.
- While elongation rates increase, RNAPII processivity decreases, leading to frequent premature termination.
- Widespread usage of intronic polyadenylation (IPA) sites occurs, driven by U1 telescripting inhibition.
- This results in the production of novel, short mRNAs that accumulate in the nucleus, reconfiguring the human transcriptome.
Conclusions:
- Heat shock induces a genome-wide shift towards intronic polyadenylation (IPA) site usage under physiological conditions.
- This mechanism contributes to the dramatic reconfiguration of the human transcriptome during heat stress.
- Findings reveal novel insights into transcription regulation at elevated temperatures.
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