Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis
- University of California, Berkeley, United States
Abstract
RNA abundance is generally sensitive to perturbations in decay and synthesis rates, but crosstalk between RNA polymerase II transcription and cytoplasmic mRNA degradation often leads to compensatory changes in gene expression. Here, we reveal that widespread mRNA decay during early apoptosis represses RNAPII transcription, indicative of positive (rather than compensatory) feedback. This repression requires active cytoplasmic mRNA degradation, which leads to impaired recruitment of components of the transcription preinitiation complex to promoter DNA. Importin a/b-mediated nuclear import is critical for this feedback signaling, suggesting that proteins translocating between the cytoplasm and nucleus connect mRNA decay to transcription. We also show that an analogous pathway activated by viral nucleases similarly depends on nuclear protein import. Collectively, these data demonstrate that accelerated mRNA decay leads to the repression of mRNA transcription, thereby amplifying the shutdown of gene expression. This highlights a conserved gene regulatory mechanism by which cells respond to threats.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Cytoplasmic mRNA decay represses RNAPII transcription during early apoptosisNCBI Gene Expression Omnibus, GSE163923.
Article and author information
Author details
Britt A Glaunsinger
Funding
National Institutes of Health (R01CA136367)
- Britt A Glaunsinger
Howard Hughes Medical Institute (n/a)
- Britt A Glaunsinger
Howard Hughes Medical Institute (Gilliam Fellowship)
- Christopher Duncan-Lewis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Duncan-Lewis et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis
eLife 10:e58342.
https://doi.org/10.7554/eLife.58342
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