Dystrophia myotonica protein kinase messenger RNA containing expanded CUG repeats (DMPK (CUG)n mRNA) (DMPK (CUG)n mRNA)

The Dystrophia myotonica protein kinase (DMPK) messenger RNA containing expanded CUG repeats is the primary pathogenic driver of Myotonic Dystrophy Type 1 (DM1) (Thornton, 2014, PMID: 24246974). In DM1, a CTG trinucleotide expansion in the 3' untranslated region (UTR) of the DMPK gene is transcribed into a toxic mRNA that forms stable hairpin structures (Miller et al., 2000, PMID: 10854425). These hairpins sequester essential RNA-binding proteins, particularly Muscleblind-like 1 (MBNL1), leading to widespread alternative splicing defects known as spliceopathy (Wheeler et al., 2012, PMID: 22810588). This molecular dysfunction results in the clinical hallmarks of DM1, including myotonia, muscle wasting, and cardiac conduction abnormalities. Therapeutic strategies targeting this molecule, such as antisense oligonucleotides (ASOs) and siRNA-based conjugates like Delpacibart zotirsen (AOC 1001), aim to degrade the toxic RNA or block its interactions with sequestered proteins (Avidity Biosciences, 2024). By reducing the burden of expanded CUG repeats, these treatments seek to restore normal RNA processing and alleviate the multisystemic symptoms of the disease (Dyne Therapeutics, 2024).

Other names

CUG-expanded DMPK mRNAToxic DMPK RNADM1 expanded repeatsDMPK 3' UTR CUG repeatsExpanded CUG repeat RNADMPK pre-mRNA containing expanded CUG repeat hairpin

Degradation of toxic expanded CUG repeat RNA via RNase H-mediated cleavage or RNA interference, and steric blocking of RNA-binding protein sequestration sites to restore normal splicing patterns.