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

TitleChanges in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription.
Publication TypeJournal Article
Year of Publication2018
AuthorsGilbertson, S, Federspiel, JD, Hartenian, E, Cristea, IM, Glaunsinger, B
JournalElife
Volume7
Date Published2018 Oct 03
ISSN2050-084X
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.

DOI10.7554/eLife.37663
Alternate JournalElife
PubMed ID30281021
Grant ListCA136367 / / National Institutes of Health /
GM114141 / / National Institutes of Health /