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Nat Struct Mol Biol. 2008 Aug;15(8):819-26. doi: 10.1038/nsmb.1461. Epub 2008 Jul 20.

The splicing factor SC35 has an active role in transcriptional elongation.

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Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.


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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