Figure 1.

Splice sites, regulatory elements and splicing alterations caused by mutations. (A) Yellow or blue boxes and black lines symbolize exons and introns respectively. The acceptor (AG) and donor (GU) sites, branch site (A), polypyrimidine (Py) tract and splicing regulatory elements (ESE, ESS, ISE, ISS) are indicated. Mutations in any of these sites could disturb pre-mRNA splicing by disruption of binding of the respective splicing factors. An SR protein and a splicing inhibitor (hnRNP) bind to an exonic splicing enhancer (ESE) and an exonic splicing silencer, respectively. The U2AF splicing factor binds to the Py tract, and this promotes binding of U2 snRNP to the branch site. U1 snRNP binds to the donor splice site. Arrows indicate protein-protein interactions between the splicing factors. (B) Examples of splicing alterations caused by mutations (indicated by vertical arrows) that affect an acceptor splice site, ESE or ISE, a mutation that generates a new acceptor site or activates a cryptic one, and a mutation that affects a donor splice site.