Stimulatory effect of splicing factors on transcriptional elongation

Transcription and pre-mRNA splicing are tightly coupled gene expression events in eukaryotic cells(1,2). An interaction between the carboxy-terminal domain of the largest subunit of RNA polymerase (Pol) II and components of the splicing machinery is postulated to mediate this coupling(3-5). Here, we show that splicing factors function directly to promote transcriptional elongation, demonstrating that transcription is more intimately coupled to splicing than previously thought. The spliceosomal U small nuclear ribonucleoproteins (snRNPs) interact with human transcription elongation factor TAT-SF1 (refs 6-9) and strongly stimulate polymerase elongation when directed to an intron-free human immunodeficiency virus-1 (HIV-1) template. This effect is likely to be mediated through the binding of TAT-SF1 to elongation factor P-TEFb(10), a proposed component of the transcription elongation complex(11,12). Inclusion of splicing signals in the nascent transcript further stimulates transcription, supporting the notion that the recruitment of U snRNPs near the elongating polymerase is important for transcription. Because the TAT-SF1-UsnRNP complex also stimulates splicing in vitro, it may serve as a dual-function factor to couple transcription and splicing and to facilitate their reciprocal activation.