Figure 2.

Cis-elements affecting splicing of MAPT exon 10. Silencer (red) and enhancer (green) sequences within and surrounding exon 10 are indicated. Exon 10 sequence is designated by capital letters and intronic sequence is indicated by small case letters. (A) Several cis-elements affect MAPT exon 10 splicing, listed 5′ to 3′: a SC35-like enhancer, a polypurine enhancer (PPE), an A/C-rich enhancer (ACE), an exonic splicing silencer (ESS), an exonic splicing enhancer (ESE), an intronic splicing silencer (ISS) and an intronic splicing modulator (ISM). Select FTDP-17 and PSP mutations are also shown. (B) Alternative splicing regulation at the tau exon 10 5′ splice site. Two of the variant stem-loop structures proposed to regulate splicing at the tau exon 5′ splice site (Hutton et al. 1998; Spillantini et al. 1998). (C) The linear model of tau exon 10 5′ splicing regulation postulates that binding of trans-acting factors to the cis-regulatory elements mediates exon 10 alternative splicing. Shown here is a trans-acting factor bound to the ISM. This ISM binding protein sterically hinders a trans-acting silencer (ISS binding protein) from binding the silencing cis-element, thereby allowing access of the U1 snRNP to the 5′ splice site (D’Souza and Schellenberg 2002; D’Souza and Schellenberg 2005).