FIG. 7.

Schematic representation of possible mechanisms involved in regulation of α-TM terminal exon utilization. The upper scheme shows that RBM4 and PTB act oppositely on exon 9a utilization of α-TM. Overexpression of RBM4 reverses the suppressive activity of PTB in exon 9a inclusion via the CU1 element (black vertical line), thus yielding the sk isoform. The lower scheme shows a possible competition between splicing and polyadenylation. We propose that the U1 snRNP and cleavage and polyadenylation specificity factor (CPSF) compete for the overlapping 5′ splice/polyadenylation site. Enhanced expression of the sk isoform by RBM4 suggests that RBM4 facilitates the interaction of the U1 snRNP with the 5′ splice site of intron 9a, thus precluding CPSF from binding to the overlapping polyadenylation signal. Expression of the 9a′ mRNA is not modulated by RBM4; however, its association with RBM4 suggests that RBM4 binds to intron 9a but is silent in splicing activation under some circumstances.