Reducing Mutant Huntingtin Protein Expression in Living Cells by a Newly Identified RNA CAG Binder

摘要: Expanded CAG trinucleotide repeats in Huntington’s disease (HD) are causative for neurotoxicity. The mutant repeat RNA encodes neurotoxic polyglutamine proteins and can lead to a toxic gain of function by aberrantly recruiting RNA-binding proteins. One these is the MID1 protein, which induces aberrant Huntingtin (HTT) protein translation upon binding. Here we have identified set binder candidates silico methods. those, furamidine, reduces level binding HTT mRNA other target vitro. Metadynamics calculations, fairly consistent with experimental data measured here, provide hints about mode ligand. Importantly, furamidine also decreases HD cell line model. This shows that small molecules masking RNA–MID1 interactions may be active against living cells.