RNA polymerase II–associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II
Author(s) -
Ming Yu,
Wenjing Yang,
Ting Ni,
Zhanyun Tang,
Tomoyoshi Nakadai,
Jun Zhu,
Robert G. Roeder
Publication year - 2015
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.aad2338
Subject(s) - rna polymerase ii , transcription factor ii f , transcription factor ii e , transcription factor ii d , rna polymerase iii , transcription (linguistics) , polymerase , rna polymerase ii holoenzyme , transcription factor ii b , rna polymerase i , microbiology and biotechnology , promoter , chemistry , biology , gene , rna dependent rna polymerase , genetics , gene expression , linguistics , philosophy
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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