The splicing factor SC35 has an active role in transcriptional elongation

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Abstract
It is known that components of the splicing machinery are guided to nascent transcripts through interactions with the Pol II transcriptional complex. Data now indicate that depletion of SC35, a splicing factor, leads to defective elongation as well as reduced Pol II phosphorylation and association with elongation factors. This leads to a model where components of the splicing machinery have a role in promoting elongation of the transcriptional machinery. 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.