Glc7/PP1 triggers Paf1 complex dissociation from RNA polymerase II to enable transcription termination.

Abstract

The mechanisms that control the dynamic composition of RNAPII elongation complexes govern major transitions in the transcription cycle yet are poorly understood. Here, we show that the transcription elongation factor Spt5 determines elongation complex composition to promote productive elongation and the transition to termination. Using an unbiased genetic screen and genomic approaches in Saccharomyces cerevisiae, we provide evidence that dephosphorylation of the Spt5 C-terminal repeat domain (CTR) by Glc7/PP1 is required to dislodge the Paf1 complex (Paf1C) from RNAPII near the cleavage and polyadenylation site (CPS). Mutations in Paf1C or the Spt5 CTR that dissociate Paf1C from RNAPII bypass the requirement for two critical regulators of Glc7 in the cleavage and polyadenylation factor that promote Glc7 enrichment at the 3' ends of genes. Depletion of Glc7 causes aberrant retention of Paf1C past the CPS and a dramatic increase in readthrough transcription, which is fully suppressed by Paf1C mutations. Our results demonstrate that Paf1C retention antagonizes transcription termination and that Glc7-mediated restructuring of the RNAPII elongation complex to evict Paf1C at the CPS is a critical step in the transition from elongation to termination.