RNA polymerase II–associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II

M Yu, W Yang, T Ni, Z Tang, T Nakadai, J Zhu… - Science, 2015 - science.org
M Yu, W Yang, T Ni, Z Tang, T Nakadai, J Zhu, RG Roeder
Science, 2015science.org
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
DRB sensitivity–inducing factor, negative elongation factor, and C-terminal domain (CTD)
serine-2 of Pol II. We found that Pol II–associated factor 1 (PAF1) is a critical regulator of
paused Pol II release, that positive transcription elongation factor b (P-TEFb) directly …
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 DRB sensitivity–inducing factor, negative elongation factor, and C-terminal domain (CTD) serine-2 of Pol II. We found that Pol II–associated factor 1 (PAF1) is a critical 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 cooperativity among P-TEFb, PAF1C, and CDK12 in pausing release and Pol II CTD phosphorylation.
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