Pre-mRNA splicing and its cotranscriptional connections.

The Pol II transcription elongation complex (TEC) makes contacts with the splicing apparatus to facilitate cotranscriptional splicing. Splicing can occur rapidly once the 3′ splice site has been synthesized, even for long introns, suggesting that exon definition is not essential. The splicing of individual introns is highly plastic, with variation in the kinetics, mode of exon:intron recognition, and the use of recursive splice sites. Nascent RNA folding into alternative structures is sensitive to the speed of transcription and may exert widespread effects on splicing. Exon-mediated activation of transcription starts (EMATS) is a means by which splicing of an alternative exon feeds back onto transcription of the same gene to activate weak promoters and select alternative mRNA 5′ ends. Transcription of eukaryotic genes by RNA polymerase II (Pol II) yields RNA precursors containing introns that must be spliced out and the flanking exons ligated together. Splicing is catalyzed by a dynamic ribonucleoprotein complex called the spliceosome. Recent evidence has shown that a large fraction of splicing occurs cotranscriptionally as the RNA chain is extruded from Pol II at speeds of up to 5 kb/minute. Splicing is more efficient when it is tethered to the transcription elongation complex, and this linkage permits functional coupling of splicing with transcription. We discuss recent progress that has uncovered a network of connections that link splicing to transcript elongation and other cotranscriptional RNA processing events. [ABSTRACT FROM AUTHOR]