1. Cell Biology
  2. Chromosomes and Gene Expression

Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis

  1. Christopher Duncan-Lewis
  2. Ella Hartenian
  3. Valeria King
  4. Britt A Glaunsinger  Is a corresponding author
  1. University of California, Berkeley, United States
https://doi.org/10.7554/eLife.58342
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  1. Christopher Duncan-Lewis
  2. Ella Hartenian
  3. Valeria King
  4. Britt A Glaunsinger
(2021)
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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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.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Author details

  1. 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.

  2. 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.

  3. 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.

  4. 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.
    ORCID icon "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

© 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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  1. Christopher Duncan-Lewis
  2. Ella Hartenian
  3. Valeria King
  4. Britt A Glaunsinger
(2021)
Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis
eLife 10:e58342.
https://doi.org/10.7554/eLife.58342

Share this article

https://doi.org/10.7554/eLife.58342

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