Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination.

Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA.

Cell 2011 Mar 4

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The Mpk1 MAPK of the yeast cell wall integrity pathway uses a noncatalytic mechanism to activate transcription of stress-induced genes by recruitment of initiation factors to target promoters. We show here that Mpk1 additionally serves a function in transcription elongation that is also independent of its catalytic activity. This function is mediated by an interaction between Mpk1 and the Paf1 subunit of the Paf1C elongation complex. A mutation in Paf1 that blocks this interaction causes a specific defect in transcription elongation of an Mpk1-induced gene, which results from Sen1-dependent premature termination through a Nab3-binding site within the promoter-proximal region of the gene. Our findings reveal a regulatory mechanism in which Mpk1 overcomes transcriptional attenuation by blocking recruitment of the Sen1-Nrd1-Nab3 termination complex to the elongating polymerase. Finally, we demonstrate that this mechanism is conserved in an interaction between the human ERK5 MAPK and human Paf1. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Ki-Young Kim, David E Levin. Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination. Cell. 2011 Mar 4;144(5):745-56