title: RNA polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II.
abstract: 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.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.affiliation: Systems Biology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ni
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Zhanyun
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Nakadai
authors.affiliation: Systems Biology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA. roeder@rockefeller.edu.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
mesh_terms: D045744:Cell Line, Tumor; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061805:Transcription Elongation, Genetic; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C501972:PAF1 protein, human; D014157:Transcription Factors; C118437:negative elongation factor; D042925:Positive Transcriptional Elongation Factor B; C447339:CDK12 protein, human; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II