Release of promoter-proximal paused RNA polymerase II (Pol II) during early elongation is a critical step in transcriptional regulation in metazoan cells. Paused Pol II release is thought to require the kinase activity of cyclin-dependent kinase 9 (CDK9) for the phosphorylation of 5,6-dichloro-1--D-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF), negative elongation factor (NELF), and C-terminal domain (CTD) serine-2 of Pol II. Here we demonstrate that RNA Polymerase II-associated factor 1 (PAF1) is a regulator of paused Pol II release, that positive transcription elongation factor b (P-TEFb) directly regulates the initial recruitment of PAF1 complex (PAF1C) to genes, and that the subsequent recruitment of CDK12 is dependent on PAF1C. These findings reveal a cooperation of P-TEFb, PAF1C, and CDK12 in pausing release and CTD phosphorylation of Pol II. SOURCE: Robert Roeder (roeder@rockefeller.edu) -  The Rockefeller University

Pluto Bioinformatics

GSE62171: RNA Polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA Polymerase II