Effect of Small Molecules on Repeat RNA Toxicity in Animal Models

Abstract

Repeat RNAs exhibit "RNA toxicity" by trapping RNA-binding proteins, thereby suppressing the proteins' native functions. The mismatch-binding molecules created in this study bound with high affinity and specificity to the slip-out structure formed by repeat DNA and RNA sequences, induced the shortening of repeat DNA length, and alleviated compound eye degeneration and splicing defects in animal models of Huntington's disease, spinocerebellar ataxia type 31, and myotonic dystrophy type 1.