Dystrophia myotonica protein kinase mRNA with expanded CUG repeats (CUGexp-DMPK) (CUGexp-DMPK)

Mutant CUGexp-DMPK transcripts are the primary pathogenic drivers of Myotonic Dystrophy Type 1 (DM1), a multisystemic neuromuscular disorder [1, 6]. These transcripts arise from an expansion of CTG repeats in the 3' untranslated region (UTR) of the DMPK gene, which are transcribed into long, repetitive CUG sequences in the mRNA [4, 20]. The expanded CUG repeats form stable hairpin structures that aggregate into nuclear ribonuclear foci, sequestering essential RNA-binding proteins such as Muscleblind-like 1 (MBNL1) [10, 15]. This sequestration leads to a global 'spliceopathy,' where hundreds of pre-mRNAs are incorrectly processed, resulting in clinical symptoms like myotonia, muscle wasting, and cardiac conduction defects [11, 13]. Therapeutic strategies focus on reducing the levels of these toxic transcripts using antisense oligonucleotides (ASOs) or siRNA, or by using small molecules to disrupt the interaction between the toxic RNA and sequestered proteins [5, 21, 23].

Other names

DMPK-CUGexpExpanded CUG repeat RNAToxic DMPK RNADM1 mRNAMutant DMPK transcripts

RNase H-mediated degradation of mRNA, RNA interference (RNAi), steric hindrance of RNA-binding protein sequestration, and small molecule-mediated RNA cleavage.