DMPK 3' UTR CUG repeat RNA (DMPK CUG repeat RNA)

The DMPK CUG repeat-containing RNA refers to the expanded trinucleotide CUG repeats in the 3'-untranslated region (3'-UTR) of the myotonic dystrophy protein kinase (DMPK) gene transcript, which is the primary pathogenic element in myotonic dystrophy type 1 (DM1), a multisystem neuromuscular disorder.[1][2][6] In DM1 patients, these repeats expand beyond 50-100 triplets (normal: 5-37), forming stable hairpin structures with length-dependent plasticity, including single asymmetrical hairpins or branched conformations, that cause nuclear retention of the mutant DMPK mRNA in discrete foci.[1][3] These RNA foci sequester RNA-binding proteins such as muscleblind-like (MBNL) family members, leading to misregulated alternative splicing of numerous transcripts and contributing to DM1 phenotypes like muscle weakness, myotonia, and cardiac issues.[2][4] The structured environment around the repeats, including a G6-clamp and GC-rich helices, isolates the CUG tract and maintains overall DMPK RNA folding despite expansion.[1] Therapeutically, this RNA is targeted by antisense oligonucleotides (AONs), siRNAs like siCAG, and gapmers, which disrupt hairpins, degrade the toxic RNA via RNase H, reduce foci, and alleviate splicing defects, with greater potency against longer expansions.[1][2][4] Ongoing research validates these approaches in cellular and mouse models of DM1.[2][5]

Other names

Expanded CUG repeats in DMPK transcriptsCUG^exp^ RNADMPK mutant RNADM1 RNA foci

RNase H-mediated degradation of toxic RNA; RNA interference (RNAi) knockdown of expanded CUG transcripts; Disruption of CUG repeat hairpin structures via base-pairing competition; Reduction of nuclear RNA foci and release of sequestered proteins like MBNL