RNA offers nearly unlimited potential as a target for small molecule chemical probes and lead medicines. Many RNAs fold into structures that can be selectively targeted with small molecules. This Perspective discusses molecular recognition of RNA by small molecules and highlights key enabling technologies and properties of bioactive interactions. Sequence-based design of ligands targeting RNA has established rules for affecting RNA targets and provided a potentially general platform for the discovery of bioactive small molecules. The RNA targets that contain preferred small molecule binding sites can be identified from sequence, allowing identification of off-targets and prediction of bioactive interactions by nature of ligand recognition of functional sites. Small molecule targeted degradation of RNA targets (ribonuclease-targeted chimeras, RIBOTACs) and direct cleavage by small molecules have also been developed. These growing technologies suggest that the time is right to provide small molecule chemical probes to target functionally relevant RNAs throughout the human transcriptome.

中文翻译：

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我们如何看待用小分子靶向 RNA。

RNA 作为小分子化学探针和先导药物的靶标具有近乎无限的潜力。许多 RNA 折叠成可以被小分子选择性靶向的结构。本视角讨论了小分子对 RNA 的分子识别，并重点介绍了生物活性相互作用的关键实现技术和特性。基于序列的 RNA 配体设计已经建立了影响 RNA 靶点的规则，并为发现生物活性小分子提供了一个潜在的通用平台。包含优选小分子结合位点的RNA靶标可以从序列中识别出来，从而可以通过配体识别功能位点的性质来识别脱靶并预测生物活性相互作用。RNA 靶标的小分子靶向降解（核糖核酸酶靶向嵌合体，RIBOTAC）和小分子直接切割也已得到开发。这些不断发展的技术表明，现在是时候提供小分子化学探针来靶向整个人类转录组中功能相关的 RNA。