Cytosine-Uracil-Guanine repeat RNA (CUG repeat RNA)

Cytosine-Uracil-Guanine (CUG) repeat RNA refers to transcripts containing expanded trinucleotide repeats that serve as the primary pathogenic driver in Myotonic Dystrophy Type 1 (DM1) and Fuchs Endothelial Corneal Dystrophy (FECD) [1, 6]. In DM1, these expansions occur in the 3' untranslated region (UTR) of the DMPK gene, while in FECD, they are found within the introns of the TCF4 gene [3, 13]. The expanded RNA sequences fold into stable hairpin structures that sequester essential RNA-binding proteins, most notably the Muscleblind-like (MBNL) family, leading to a toxic gain-of-function [1, 8]. This sequestration results in widespread alternative splicing defects, or "splicopathy," affecting genes critical for muscle, cardiac, and neurological function [13, 15]. Therapeutic strategies focus on neutralizing this toxic RNA using antisense oligonucleotides (ASOs) to trigger its degradation or small molecules designed to displace MBNL proteins and restore normal splicing patterns [7, 11].

Other names

r(CUG)expExpanded CUG repeat RNAToxic CUG RNADMPK CUG repeat RNAMicrosatellite RNA

Drugs targeting CUG repeat RNA primarily work through antisense-mediated RNase H cleavage to degrade the toxic transcripts, or via small molecules that displace sequestered RNA-binding proteins and facilitate RNA decay through the nuclear exosome complex.