RNA pull-down-Confocal Nanoscanning (RP-CONA) detects quercetin as pri-miR-7/HuR interaction inhibitor that decreases α-Synuclein levels

RNA–protein interactions are central to all gene expression processes and contribute to a variety of human diseases. Therapeutic approaches targeting RNA–protein interactions have shown promising effects on some diseases that are previously regarded as ‘incurable’. Here, we developed a fluorescent on bead screening platform, RNA Pull-Down COnfocalNAnoscanning (RP-CONA), to identify RNA–protein interaction modulators in eukaryotic cell extracts. Using RP-CONA, we identified small molecules that disrupt the interaction between HuR, an inhibitor of brain-enriched miR-7 biogenesis, and the conserved terminal loop of pri-miR-7–1. Importantly, miR-7s primary target is an mRNA of -synuclein, which contributes to the aetiology of Parkinson’s disease. Our method identified a natural product quercetin as a molecule able to upregulate cellular miR-7 levels and down regulate the expression of -synuclein. This opens up new therapeutic avenues towards treatment of Parkinson’s disease as well as provides a novel methodology to search for modulators of RNA–protein interaction.