Figure 10.

Models for the role of ISE pairs in exon definition. (a) Proteins binding the co-occurring motif ISE pairs specifically interact with each other as well as factors such as SR proteins binding to two ESEs. This tetrapartite complex can recruit the initial components of the splicing machinery, U1 small nuclear ribonucleoprotein (snRNP) and U2AF, to produce an exon definition complex in which the two ends of the exon are brought together, with much of the exon looped out. It is this complex that can undergo subsequent steps leading to intron definition and splicing. If any one of the four components is missing, the complex is too unstable and efficient recruitment is not realized. (b) Proteins binding the co-occurring motif ISE pairs interact specifically with factors such as SR proteins bound to terminally located ESEs. The ESE bound factors interact with additional ESE-binding factors so as to span the entire exon, and it is this exon-wide complex that represents exon definition. The loss of any one component results in destabilization of the complex and loss of exon definition. In either model, some exons may require ISEs and their binding proteins for sufficient stabilization while for others strong ESEs may suffice.