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

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.