RNA-protein interactions are central to all gene expression processes and contribute to 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-Confocal Nanoscanning (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-7′s primary target is an mRNA of α-Synuclein, which contributes to aetiology of Parkinson′s disease. Our method identified a natural product quercetin as a molecule able to upregulate cellular miR-7 levels and downregulate the expression of α-Synuclein. This opens up new therapeutic avenues towards treatment of Parkinson′s disease as well as provides novel methodology to search for RNA-protein interaction modulators.

中文翻译：

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RNA下拉-Confocal纳米扫描（RP-CONA）将槲皮素检测为pri-miR-7 / HuR相互作用抑制剂，可降低α-突触核蛋白的水平

RNA-蛋白质相互作用是所有基因表达过程的核心，并导致多种人类疾病。针对RNA-蛋白质相互作用的治疗方法已显示出对某些以前被认为是“无法治愈”的疾病的有希望的效果。在这里，我们开发了一种荧光珠子筛选平台：RNA下拉-Confocal纳米扫描（RP-CONA），以鉴定真核细胞提取物中的RNA-蛋白质相互作用调节剂。使用RP-CONA，我们发现了破坏HuR（一种富含脑的miR-7生物发生的抑制剂）与pri-miR-7-1保守的末端环之间的相互作用的小分子。重要的是，miR-7的主要靶标是α-突触核蛋白的mRNA，它有助于帕金森氏病的病因学。我们的方法将天然产物槲皮素鉴定为能够上调细胞miR-7水平并下调α-突触核蛋白表达的分子。这为治疗帕金森氏病开辟了新的治疗途径，并提供了寻找RNA-蛋白质相互作用调节剂的新方法。