Expanded CUG repeat RNA

Expanded CUG repeat RNA refers to abnormally long stretches of cytosine–uracil–guanine trinucleotide repeats found within the 3′ untranslated region (UTR) of certain mRNAs, most notably the DMPK gene transcript associated with myotonic dystrophy type 1 (DM1)[2][5]. These expanded repeats form highly stable hairpin secondary structures characterized by periodic U-U mismatches within an otherwise A-form double helix. The abnormal structure sequesters key regulatory proteins such as Muscleblind-like protein 1 (MBNL1), leading to widespread defects in pre-mRNA splicing and other aspects of post-transcriptional regulation[3][4][5]. Additionally, these RNAs can activate double-stranded-RNA binding proteins like PKR, triggering stress responses that further inhibit translation and contribute to disease pathology[1][6]. Therapeutic strategies are being developed that target these toxic RNAs using small molecules or antisense oligonucleotides designed either to disrupt their structure or promote their degradation. The length and presence of expanded CTG/CUG repeats serve as both a diagnostic marker for DM1 and a potential biomarker for therapeutic intervention efficacy. However, achieving selectivity without affecting normal cellular processes remains a significant challenge in drug development targeting this pathogenic non-coding RNA species.

Other names

CUG repeat expansion RNAr(CUG)expExpanded CUG repeats in DMPK mRNAPathogenic CUG repeat RNA

Small molecule or oligonucleotide binding to expanded CUG repeats disrupts pathogenic hairpin structures or promotes cleavage/removal, thereby releasing sequestered proteins and restoring normal splicing/translation[3]