Dystrophia myotonica protein kinase mRNA CUG repeat (DMPK mRNA CUG repeat)

The Dystrophia myotonica protein kinase (DMPK) mRNA CUG repeat is the pathogenic driver of Myotonic Dystrophy type 1 (DM1), a multisystemic genetic disorder. In DM1, the 3' untranslated region of the DMPK gene contains an expanded CTG trinucleotide repeat that is transcribed into a toxic mRNA containing expanded CUG repeats. These repeats form stable secondary structures that sequester RNA-binding proteins, particularly the Muscleblind-like (MBNL) family, into nuclear ribonuclear foci. The resulting depletion of functional MBNL proteins leads to widespread mis-splicing of downstream pre-mRNAs, causing clinical manifestations such as myotonia, muscle wasting, and cardiac defects. Therapeutic approaches focus on reducing the levels of the toxic mutant mRNA or preventing the sequestration of splicing factors using antisense oligonucleotides, siRNAs, or small molecules. Recent clinical developments include antibody-oligonucleotide conjugates and peptide-conjugated morpholinos designed to improve delivery to muscle tissues.

Other names

DMPK CUG expansionCUGexpToxic DMPK mRNACUG repeat RNADM1 repeat expansionDMPK 3' UTR repeat

RNA interference (siRNA), RNase H-mediated degradation, Steric hindrance (blocking protein sequestration), Small molecule binding to RNA secondary structures