Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription
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.
Mass spectrometry proteomics data reported in this paper have been deposited at the ProteomeXchange Consortium via the PRIDE partner repository under accession number PXD009487.
Article and author information
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.
- Torben Heick Jensen, Aarhus University, Denmark
- Received: April 18, 2018
- Accepted: September 28, 2018
- Accepted Manuscript published: October 3, 2018 (version 1)
- Version of Record published: October 26, 2018 (version 2)
© 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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