title: SR proteins collaborate with 7SK and promoter-associated nascent RNA to release paused polymerase.
abstract: RNAP II is frequently paused near gene promoters in mammals, and its transition to productive elongation requires active recruitment of P-TEFb, a cyclin-dependent kinase for RNAP II and other key transcription elongation factors. A fraction of P-TEFb is sequestered in an inhibitory complex containing the 7SK noncoding RNA, but it has been unclear how P-TEFb is switched from the 7SK complex to RNAP II during transcription activation. We report that SRSF2 (also known as SC35, an SR-splicing factor) is part of the 7SK complex assembled at gene promoters and plays a direct role in transcription pause release. We demonstrate RNA-dependent, coordinated release of SRSF2 and P-TEFb from the 7SK complex and transcription activation via SRSF2 binding to promoter-associated nascent RNA. These findings reveal an unanticipated SR protein function, a role for promoter-proximal nascent RNA in gene activation, and an analogous mechanism to HIV Tat/TAR for activating cellular genes.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Ji
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shatakshi
authors.initials: S
authors.lastname: Pandit
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Hairi
authors.initials: H
authors.lastname: Li
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Lin
authors.forename: Rui
authors.initials: R
authors.lastname: Xiao
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
mesh_terms: D000818:Animals; D004742:Enhancer Elements, Genetic; D055785:Gene Knockdown Techniques; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism*; D022661:RNA, Untranslated / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D061805:Transcription Elongation, Genetic; D061785:Transcription Initiation, Genetic; D015533:Transcriptional Activation
chemical_list: D009687:Nuclear Proteins; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C499372:SRSF2 protein, mouse; D000068103:Serine-Arginine Splicing Factors; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II