4.5 Article

The splicing factor SC35 has an active role in transcriptional elongation

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NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 15, 期 8, 页码 819-826

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NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1461

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  1. NIGMS NIH HHS [F32 GM077907-02, R01 GM049369, 5R01 GM49369, R01 GM049369-15, R01 GM049369-08, 1F32 GM077907, F32 GM077907] Funding Source: Medline

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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.

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