RT Journal Article
SR Electronic
T1 Global changes in mRNA abundance drive differential shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 295972
DO 10.1101/295972
A1 Sarah Gilbertson
A1 Joel D. Federspiel
A1 Ella Hartenian
A1 Ileana M. Cristea
A1 Britt Glaunsinger
YR 2018
UL http://biorxiv.org/content/early/2018/04/06/295972.abstract
AB Alterations in global mRNA decay broadly impact upstream and downstream 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 cytoplasmic poly(A) binding protein in repressing mammalian RNA polymerase II transcription upon its mRNA decay-induced translocation to the nucleus. 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.