Dystrophin pre-mRNA exon 2 splice sites (DMD exon 2 splice sites)

The DMD pre-mRNA splice donor and acceptor sites flanking exon 2 are critical regulatory sequences within the dystrophin gene transcript that dictate the inclusion of exon 2 during RNA splicing (UniProt P11532). These sites are recognized by the spliceosome, a complex molecular machine that removes introns and joins exons to form mature mRNA. In patients with Duchenne Muscular Dystrophy (DMD) harboring an exon 2 duplication—the most common duplication in the DMD gene—these sites serve as therapeutic targets for exon-skipping strategies (Flanigan et al., 2011, Annals of Neurology). By blocking these sites using antisense oligonucleotides (AONs) or modified small nuclear RNAs like U7 snRNA, the splicing machinery can be induced to skip the redundant exon, thereby restoring the correct reading frame (Wein et al., 2014, Nature Medicine). This restoration allows for the production of a functional, full-length or near-full-length dystrophin protein, which is essential for maintaining muscle fiber integrity. This precision medicine approach is currently being investigated in clinical trials to treat the underlying genetic cause of muscle degeneration in this specific patient population (NCT04240314).

Other names

DMD exon 2 splice donor and acceptor sitesDystrophin exon 2 splice junctionsDMD pre-mRNA exon 2 flanking sequencesDMD exon 2 splice boundaries

Exon skipping via steric hindrance of the spliceosome at the exon 2 donor and acceptor sites (Wein et al., 2014, Nature Medicine).