Figure 7.
Model for the regulation of TTN241-3 splicing by RBM20 and PTB4. (A) In the absence of RBM20, spliceosomal complexes form over the exon and over the both introns (solid arrows) to include titin exon 242. Constitutive exons in dark gray, alternative exon 242 light gray and introns are indicated as thin lines. (B) Model of RBM20 mediated exclusion of exon 242: RBM20 binds downstream intron sequences and interferes with exon 242 5′ss recognition by the U1 snRNP resulting in reduced recognition of the downstream intron. This interaction destabilizes the upstream 3′ss recognition by the U2 snRNP and interferes with the exon definition complex and upstream intron recognition. As a result, the spliceosome recognizes only the external 5′ and 3′ splice sites and exon 242 is excluded. Transparent arrows indicate absent or incomplete communication between splice sites. (C) Addition of PTB4 overcomes the negative effect of RBM20 on exon retention as both factors bind the downstream intron, where they differentially interfere with U1 snRNP and 5′ss interactions, formation of the exon definition complex and subsequent inclusion of the alternative exon.