Bidirectional RNA pairing model for coordinating mutually exclusive splicing. (A) Bidirectional pairing model. Symbols used are the same as those in Figure 1. The dashed gray arrow is depicted as the potential pairing interaction. For an alternative exon B to be included in the mature mRNA, either of the docking sites alternately interacts with their selector sequence. For example, when the Us pairs with the Dd, the RNA pairing interaction functions to promote the recognition of the weak splice site, thereby activating the splicing of exon B1 to constitutive exon C. In this case, only the exon B1 variant is included in the mRNA, because the remaining exon B2 might be actively repressed by downstream pairing in combination with other players such as weak or suboptimal splice sites (yellow circle) and splicing repressors (red oval). While the Ud pairs with the Ds, such RNA pairing interactions serve to activate or enhance the inclusion of alternative exon B2. Alternatively, both pairs occur simultaneously through the formation of a long-range pseudoknot. In this case, the more quickly spliced exon would be included in the mRNA, while the other is spliced out. (B) Upstream pairing (red) and downstream pairing (blue) are competitive but regulate the inclusion of the alternative exon.
