Dystrophin pre-messenger RNA splice sites (DMD pre-mRNA) (DMD pre-mRNA)

Dystrophin pre-messenger RNA (pre-mRNA) splice sites are the specific sequences at the boundaries of exons and introns within the DMD gene transcript that are recognized by the spliceosome (UniProt P11532). These sites are critical for the correct assembly of the dystrophin mRNA, which encodes a protein essential for maintaining the structural integrity of muscle fibers (StatPearls, 2023). In Duchenne muscular dystrophy (DMD), mutations often disrupt the reading frame, leading to a lack of functional dystrophin and progressive muscle wasting (NIH, 2023). Therapeutic antisense oligonucleotides (ASOs) are designed to bind to these splice sites or nearby exonic splicing enhancers to sterically block the splicing machinery (PubMed: 22441781). This intervention induces "exon skipping," which bypasses the mutated region and restores the reading frame, resulting in the production of a truncated but functional dystrophin protein (PubMed: 28435515). Drugs such as eteplirsen, golodirsen, and viltolarsen target these sites to treat specific genetic subsets of DMD patients (FDA, 2016, 2019, 2020).

Other names

DMD pre-mRNADystrophin exon-intron junctionsDystrophin splicing regulatory elements

Antisense oligonucleotides bind to specific sequences within the pre-mRNA (such as splice sites or exonic splicing enhancers) to sterically block the splicing machinery, resulting in the exclusion of specific exons (exon skipping) to restore the open reading frame.