Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis

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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.

The following data sets were generated

(2020) Cytoplasmic mRNA decay represses RNAPII transcription during early apoptosis
NCBI Gene Expression Omnibus, GSE163923.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE163923

Article and author information

Author details

Christopher Duncan-Lewis

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Ella Hartenian

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Valeria King

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Britt A Glaunsinger

Department of Plant & Microbial Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
glaunsinger@berkeley.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0479-9377

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

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.