The yeast checkpoint kinase Mec1p functions in transcription termination by facilitating recruitment of Pcf11p and regulating the torpedo exonuclease Rat1p

Transcription cycle of RNA polymerase II (RNAPII) features three stages: initiation, elongation, and termination. Termination, closely linked with pre-mRNA 3' processing, dissociates RNAPII from DNA and releases the nascent RNA transcript. Efficient termination is required for maintaining a pool of RNAPII that is available for re-entry into new transcription cycle. Previous results showed that inactivation of checkpoint kinase Mec1p in the absence of exogenous genotoxic stress downregulates the efficiency of transcription termination and reduces the efficiency of pre-mRNA cleavage at the polyadenylation (pA) sites. We report here that Mec1p impacts transcription termination at two distinct steps. Mec1p promotes recruitment of Pcf11p, a subunit of the cleavage factor IA (CF IA), to 3' ends of genes, and regulates the activity of torpedo exonuclease Rat1p. Deletion of Mec1p or mutations that prevent activation of Mec1p partially suppress both transcription termination defects as well as rRNA and snoRNA processing defects in rat1-1 cells. These results suggest that Mec1p regulates features of Rat1p function that are shared by termination of RNAPII transcription and rRNA and snoRNA processing and imply that the kinase activity of Mec1p downregulates Rat1p function. Cumulatively, our results reveal a new role for checkpoint kinase Mec1p in transcription termination and regulation of the torpedo exonuclease Rat1p.