title: The splicing factor SC35 has an active role in transcriptional elongation.
abstract: Mounting evidence suggests that transcription and RNA processing are intimately coupled in vivo, although each process can occur independently in vitro. It is generally thought that polymerase II (Pol II) C-terminal domain (CTD) kinases are recruited near the transcription start site to overcome initial Pol II pausing events, and that stably bound kinases facilitate productive elongation and co-transcriptional RNA processing. Whereas most studies have focused on how RNA processing machineries take advantage of the transcriptional apparatus to efficiently modify nascent RNA, here we report that a well-studied splicing factor, SC35, affects transcriptional elongation in a gene-specific manner. SC35 depletion induces Pol II accumulation within the gene body and attenuated elongation, which are correlated with defective P-TEFb (a complex composed of CycT1-CDK9) recruitment and dramatically reduced CTD Ser2 phosphorylation. Recombinant SC35 is sufficient to rescue this defect in nuclear run-on experiments. These findings suggest a reciprocal functional relationship between the transcription and splicing machineries during gene expression.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.
authors.forename: Shengrong
authors.initials: S
authors.lastname: Lin
authors.forename: Gabriela
authors.initials: G
authors.lastname: Coutinho-Mansfield
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Shatakshi
authors.initials: S
authors.lastname: Pandit
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D012319:RNA Polymerase II / Q000737:chemistry; D012326:RNA Splicing; D011994:Recombinant Proteins / Q000737:chemistry; D012261:Ribonucleoproteins / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D014158:Transcription, Genetic
chemical_list: D009687:Nuclear Proteins; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; C499372:SRSF2 protein, mouse; D000068103:Serine-Arginine Splicing Factors; D012313:RNA; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II