The yeast checkpoint kinase Mec1p promotes Nrd1p-Nab3p-Sen1p-mediated transcription termination and attenuation

Transcription cycle of RNA polymerase II (RNAPII) features three stages: initiation, elongation, and termination. Termination, closely linked with RNA 3’ end 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. RNAPII transcription termination of most mRNAs and non-coding RNAs in S. cerevisiae occurs via polyadenylation-dependent and Nrd1p-Nab3p-Sen1p (NNS)-dependent pathways, respectively. Previous results showed that checkpoint kinase Mec1p in the absence of exogenous genotoxic stress promotes transcription termination by the polyadenylation-dependent pathway by facilitating recruitment of termination factor Pcf11p and torpedo exonuclease Rat1p to 3’ ends of genes. We report here that Mec1p is required also for efficient NNS-mediated termination. Mec1p inactivation causes transcription read-through of snoRNAs, downregulates the efficiency of NNS-mediated transcription termination, and enhances growth defect in cells with compromised NNS complex. Mec1p also promotes the NNS-mediated transcription attenuation. However, Mec1p is not required for phosphorylation of the carboxy-terminal domain of the largest RNAPII subunit Rpb1p at Ser5 and for recruitment of Nrd1p to 5’ ends of genes. Together, our data reveal a new role for checkpoint kinase Mec1p in NNS-mediated transcription termination and suggest that during S phase, Mec1p enforces efficient transcription termination of both mRNAs and non-coding RNAs, perhaps to limit transcription-replication conflicts.