Nuclear translocation of RNA binding proteins links accelerated cytoplasmic mRNA decay and transcription
- Author(s): Gilbertson, Sarah
- Advisor(s): Glaunsinger, Britt
- et al.
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. 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 TATA-binding protein and RNA polymerase II transcription upon its mRNA decay-induced translocation to the nucleus.
We identified PABPC nuclear-specific protein-protein interactions, and found a number of interactions with proteins involved in the ubiquitin-proteasome system. Two of these protein partners were required to maintain the mRNA decay-transcription feedback pathway. Furthermore, mRNA decay initiated using the decapping enzyme, D10 from vaccinia virus, revealed that this system did not depend on the process by which the accelerated mRNA decay was initiated and instead is responsive to broad changes in mRNA abundance. In addition, we found that PABPC nuclear translocation was not affected by Dis3L2. Together with the finding that PABPC nuclear accumulation alone was not sufficient to repress nascent mRNA synthesis by RNAPII, these data provide evidence that another unknown factor is required, along with PABPC, to fulfill the feedback loop.
Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein subcellular localization, providing a mechanism to connect seemingly distal stages of gene expression.