1. Chromosomes and Gene Expression
  2. Microbiology and Infectious Disease

Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription

  1. Sarah Gilbertson
  2. Joel D Federspiel
  3. Ella Hartenian
  4. Ileana M Cristea
  5. Britt Glaunsinger  Is a corresponding author
  1. University of California, Berkeley, United States
  2. Princeton University, United States
https://doi.org/10.7554/eLife.37663
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  1. Sarah Gilbertson
  2. Joel D Federspiel
  3. Ella Hartenian
  4. Ileana M Cristea
  5. Britt Glaunsinger
(2018)
Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription
eLife 7:e37663.
https://doi.org/10.7554/eLife.37663
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Abstract

Alterations in global mRNA decay broadly impact multiple stages of gene expression, although signals that connect these processes are incompletely defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to reveal that changing the mRNA decay landscape, as frequently occurs during viral infection, results in subcellular redistribution of RNA binding proteins (RBPs) in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited changes in the localization or abundance of numerous factors linked to mRNA turnover. Using these data, we uncovered a new role for relocalized cytoplasmic poly(A) binding protein in repressing recruitment of TATA binding protein and RNA polymerase II to promoters. Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein localization, providing a mechanism to connect seemingly distal stages of gene expression.

Data availability

Mass spectrometry proteomics data reported in this paper have been deposited at the ProteomeXchange Consortium via the PRIDE partner repository under accession number PXD009487.

The following data sets were generated

Article and author information

Author details

  1. Sarah Gilbertson

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Joel D Federspiel

    Department of Molecular Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. 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.

  4. Ileana M Cristea

    Department of Molecular Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Britt Glaunsinger

    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 (CA136367)

  • Britt Glaunsinger

Howard Hughes Medical Institute

  • Britt Glaunsinger

National Institutes of Health (GM114141)

  • Ileana M Cristea

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Torben Heick Jensen, Aarhus University, Denmark

Version history

  1. Received: April 18, 2018
  2. Accepted: September 28, 2018
  3. Accepted Manuscript published: October 3, 2018 (version 1)
  4. Version of Record published: October 26, 2018 (version 2)

Copyright

© 2018, Gilbertson 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. Sarah Gilbertson
  2. Joel D Federspiel
  3. Ella Hartenian
  4. Ileana M Cristea
  5. Britt Glaunsinger
(2018)
Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription
eLife 7:e37663.
https://doi.org/10.7554/eLife.37663

Share this article

https://doi.org/10.7554/eLife.37663

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