Figure 7.

Model of ISE function: the ISE facilitates processing of the splicing intermediate. In WT context binding of U1 snRNP to the ISPE element interferes with the recognition of the nearby upstream cryptic 3′ss and no preS1 intermediate is produced leading to normal processing of the intron. In the affected patient, the natural deletion (Δ) relieves the steric interference of the U1 snRNP and activates the cryptic 3′ss resulting in the generation of the preS1 intermediate. In the presence of the ISE this intermediate is processed to the mature mRNA that contains the cryptic exon whereas in the absence of it (ΔISE) the preS1 is not further processed and gets accumulated. At the preS1 level, ISE could interact with several splicing factors that assist U1snRNP recognition at the cryptic 5′ss.