Small-molecule cleavage of r(CUG)exp. (A) DM1 is caused by r(CUG)exp, located in the 3′ UTR of the DMPK gene, which forms a structure with repeating 1 × 1 U/U internal loops. The loops bind and sequester MBNL1, resulting in nuclear foci and pre-mRNA splicing defects. (B) MBNL1 protein regulates the splicing of its own pre-mRNA. When MBNL1 is sequestered by r(CUG)exp, its exon 5 is included too frequently. (C) Scheme of small-molecule cleavage of r(CUG)exp, resulting in improvement of DM1-associated defects.