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Reciprocal coupling: how splicing affects transcription
- Multiple links between transcription and splicing

Fong and Zhou (2002)Go have found that spliceosomal U small nuclear ribonucleoproteins (UsnRNPs) interact with the human transcription elongation factor TAT-SF1 and strongly stimulate pol II elongation, probably via the binding of TAT-SF1 to the elongation factor P-TEFb. Because the TAT-SF1–UsnRNP complex also stimulates splicing in vitro, these results not only reveal that splicing factors function directly to promote transcriptional elongation but that reciprocal interactions exist in the coupling process. Consistently, the presence of an intron or simply a 5'-splice site immediately downstream from a promoter greatly enhances transcription, both in mammalian and yeast genes (Furger et al. 2002Go), which indicates that factors controlling intron removal are important for normal levels of transcription. This confirms old observations of inefficient expression of recombinant cDNAs transfected into mammalian cells, compared with the corresponding intron-containing constructs. Although the underlying mechanism for the positive influence of splicing on transcription is still unknown, these results provide further support that both processes are tightly coupled. The authors favor an RNA-mediated process in which the nascent transcript, associated with splicing factors that, in turn, associate with components of the transcription machinery, promotes transcriptional elongation and perhaps regulates initiation. Such a mechanism is supported by the unexpected finding that U1 snRNA associates with the general transcription factor TFIIH, functioning in regulating transcription by pol II in addition to its role in splicing (Kwek et al. 2002Go). In addition, U1 snRNP is recruited cotranscriptionally in vivo to intron-containing genes in yeast (Kotovic et al. 2003Go). High levels of U1 snRNP were detected in intronic regions of actively transcribing genes, but not in promoter regions or along the length of intron-less genes. This kind of cotranscriptional recruitment is clearly different from the one demonstrated for capping enzymes, which bind directly to the CTD of pol II. This opens the question whether the coupling between transcription and splicing is based on the recruitment of splicing factors to the CTD or to intron-containing nascent transcripts, as shown for U1 snRNP. The latter seems to be the case at least in yeast, where it was demonstrated that the CTD is dispensable for efficient splicing.

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