The Yeast 5′-3′ Exonuclease Rat1p Functions during Transcription Elongation by RNA Polymerase II

Termination of RNA polymerase II (RNAPII) transcription of protein-coding genes occurs downstream of cleavage/polyadenylation sites. According to the “torpedo” model, the 5′-3′ exonuclease Rat1p/Xrn2p attacks the newly formed 5′ end of the cleaved pre-mRNA, causing the still transcribing RNAPII to terminate. Here we demonstrate a similar role of S. cerevisiae Rat1p within the gene body. We find that the transcription processivity defect imposed on RNAPII by the rpb1-N488D mutation is corrected upon Rat1p inactivation. Importantly, Rat1p-dependent transcription termination occurs upstream the polyadenylation site. Genetic and biochemical evidence demonstrate that mRNA capping is defective in rpb1-N488D cells, which leads to increased levels of Rat1p all along the gene locus. Consistently, Rat1p-dependent RNAPII termination is also observed in the capping-deficient ceg1-63 strain. Our data suggest that Rat1p serves to terminate RNAPII molecules engaged in the production of uncapped RNA, regardless of their position on the gene locus. [Display omitted] ► 5′-3′ exonuclease Rat1p promotes transcription termination upstream of a pA site ► Rat1p exercises quality control of mRNAs whose capping is compromised ► Capping deficiency increases recruitment of Rat1p to the gene coding region ► A slow RNA polymerase partially suppresses rat1-1 transcription termination defect