Dystrophin exon 51 pre-mRNA splicing regulatory sites (DMD exon 51 SREs)

Dystrophin exon 51 pre-mRNA splicing regulatory sites are specific sequences within the primary transcript of the DMD gene that facilitate the inclusion of exon 51 into the mature messenger RNA. These sites, primarily exonic splicing enhancers (ESEs), are essential for the correct assembly of the spliceosome during the processing of the dystrophin pre-mRNA (PubMed: 27657115). In Duchenne muscular dystrophy (DMD), mutations such as deletions of adjacent exons (e.g., exons 45-50) disrupt the reading frame, leading to a complete lack of functional dystrophin protein and progressive muscle degeneration (NIH: NBK1119). Therapeutic antisense oligonucleotides, such as Eteplirsen (Exondys 51), are designed to bind to these regulatory sites and mask them from the splicing machinery (FDA: Exondys 51 Label). This intervention induces "exon skipping," which removes exon 51 from the final transcript and restores the open reading frame. The resulting truncated dystrophin protein, while shorter than the wild-type version, retains sufficient function to stabilize muscle membranes and slow the progression of the disease (Sarepta Therapeutics).

Other names

DMD exon 51 splicing enhancerDystrophin pre-mRNA exon 51Exon 51 of the dystrophin geneExonic splicing enhancer of DMD exon 51

Antisense oligonucleotides bind to specific exonic splicing enhancers (ESEs) within the pre-mRNA to sterically block the recognition of exon 51 by the spliceosome, inducing exon skipping and restoring the translational reading frame.