Proteomics

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Global changes in mRNA abundance drive differential shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription


ABSTRACT: Alterations in global mRNA decay can broadly impact multiple upstream and downstream stages of gene expression. For example, accelerated cytoplasmic mRNA degradation can trigger a reduction in mammalian RNA polymerase II (RNAPII) transcription, although signals that connect these seemingly distal processes remain largely unknown. Here, we used tandem mass tag labeling with mass spectrometry to chart how changes in Xrn1-dependent mRNA degradation impact nuclear-cytoplasmic protein distribution in human cells. Notably, accelerating mRNA decay through expression of a gammaherpesviral endonuclease known to coordinate with Xrn1 drove nuclear relocalization of many RNA binding proteins. Particularly enriched in the relocalized subset were factors linked to the poly(A) tail. Conversely, cells lacking Xrn1 exhibited changes in the localization and/or abundance of numerous factors linked to mRNA turnover. Based on these data, we uncovered a new role for cytoplasmic poly(A) binding protein in repressing RNAPII transcription upon its mRNA decay-induced translocation to the nucleus.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo sapiens  

TISSUE(S): Cell Culture

DISEASE(S): Not Available

SUBMITTER: Joel Federspiel  

LAB HEAD: Ileana M Cristea

PROVIDER: PXD009487 | Pride | 2018-10-24

REPOSITORIES: pride

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

Gilbertson Sarah S   Federspiel Joel D JD   Hartenian Ella E   Cristea Ileana M IM   Glaunsinger Britt B  

eLife 20181003


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 d  ...[more]

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