The splicing factor SC35 has an active role in transcriptional elongation.
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.
Lin
Shengrong
S
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.
Coutinho-Mansfield
Gabriela
G
Wang
Dong
D
Pandit
Shatakshi
S
Fu
Xiang-Dong
XD
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
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