Introduction to cotranscriptional RNA splicing

Abstract

The discovery that many intron-containing genes can be cotranscriptionally spliced has led to an increased understanding of how splicing and transcription are intricately intertwined. Cotranscriptional splicing has been demonstrated in a number of different organisms and has been shown to play roles in coordinating both constitutive and alternative splicing. The nature of cotranscriptional splicing suggests that changes in transcription can dramatically affect splicing, and new evidence suggests that splicing can, in turn, influence transcription. In this chapter, we discuss the mechanisms and consequences of cotranscriptional splicing and introduce some of the tools used to measure this process.

Fig. 1

Coupling between pre-mRNA splicing and transcription. Components of the splicing machinery localize to the nascent RNA while transcription is occurring. SR proteins (blue ovals) facilitate cross talk between the CTD tail of RNA polymerase II and the splicing machinery. Cross talk also occurs between the splicing machinery and modified histones. Other RNA processing events, such as 5′ capping, also occur cotranscriptionally

Fig. 2

Kinetic Model of Cotranscriptional Splicing. (a) In Saccharomyces cerevisiae, RNA Pol II pauses at the terminal exon and/or 3′ SS to facilitate cotranscriptional splicing. (b) RNA Pol II rate of elongation modulates cotranscriptional alternative splicing. Fast elongation rate of transcription (left) favors skipping of exons with “weak” upstream 3′ splice sites (blue exon). Slower Pol II elongation rates (right) favor inclusion of exons with weak 3′ SS sites. Constitutive exons (containing strong 3′ SS) are included independently of RNA Pol II elongation rate (not shown)