Expansion of CUG repeat in DMPK mRNA

Expansion of CUG repeat in DMPK mRNA refers to an abnormally long trinucleotide (CTG/CUG) repeat expansion located in the 3′ untranslated region (UTR) of the DMPK (dystrophia myotonica protein kinase) gene transcript. In individuals with myotonic dystrophy type 1 (DM1), mutant DMPK transcripts containing several hundred to several thousand CUG repeats form stable RNA hairpins in the cell nucleus, which sequester RNA-binding proteins such as muscleblind-like 1 (MBNL1). This sequestration disrupts normal pre-mRNA splicing, leading to widespread splicing defects, impairment of mRNA export, nuclear RNA foci, stress granule formation, and ultimately multisystem pathology characteristic of DM1—including muscle weakness, cardiac defects, and cataract. The pathogenic RNA structure itself is the therapeutic target, and approaches under investigation include small molecules (e.g., Cugamycin), antisense oligonucleotides, and other modalities aimed at specifically degrading or disrupting the toxic expanded CUG repeat RNA without affecting normal DMPK function[1][2][3][4][5][6][7].

Other names

DMPK CUG repeat expansionDMPK (CUG)n expansionToxic RNA CUG repeats in DMPKr(CUG)exp in DMPK

Disruption or binding to expanded CUG repeat hairpin to prevent sequestration of RNA-binding proteins; RNA cleavage/degradation of toxic expanded CUG repeat transcript; Inhibition of mutant DMPK mRNA transcription