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

Abstract
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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

(2018) Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription
PXD009487.

http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD009487

Article and author information

Author details

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.
Joel D Federspiel

Department of Molecular Biology, Princeton University, Princeton, 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.
Ileana M Cristea

Department of Molecular Biology, Princeton University, Princeton, United States

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

"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.

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.