The splicing factor SC35 has an active role in transcriptional elongation

被引:287
作者
Lin, Shengrong [1 ,2 ]
Coutinho-Mansfield, Gabriela [1 ]
Wang, Dong [1 ]
Pandit, Shatakshi [1 ]
Fu, Xiang-Dong [1 ]
机构
[1] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Mol Pathol Grad Program, La Jolla, CA 92093 USA
关键词
D O I
10.1038/nsmb.1461
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:819 / 826
页数:8
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