Mpk1 MAPK Association with the Paf1 Complex Blocks Sen1-Mediated Premature Transcription Termination

SummaryThe 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (304 K)Download as PowerPoint slideHighlights► Yeast MAPK (Mpk1) uses a noncatalytic mechanism to block transcription attenuation ► Mpk1 affects attenuation by binding Paf1 subunit of the Paf1 elongation complex ► Mpk1-Paf1 interaction blocks recruitment of Sen1-Nrd1-Nab3 termination complex ► This mechanism is conserved in an interaction between human ERK5 MAPK and human Paf1