非编码RNA化学修饰检测新技术的发展及应用

与DNA修饰和组蛋白修饰一样，转录后修饰极大地丰富了RNA的结构与功能。近年来，以RNA化学修饰为研究对象的“表观转录组学”领域得到了科学家广泛的关注；然而，含量较低的非编码RNA—尤其是长链非编码RNA—是否也存在化学修饰，目前知之甚少。本课题组之前已经开发了针对两种RNA化学修饰（假尿嘧啶和1-甲基腺嘌呤）的表观转录组测序技术，并且发现在MALAT1、NEAT1、XIST等长链非编码RNA上存在假尿嘧啶和1-甲基腺嘌呤的化学修饰。本项目拟在前期工作的基础上，开发全转录组水平上鉴定长链非编码RNA化学修饰的新技术；同时，通过位点特异（locus-specific）的RNA修饰检测新方法，鉴定非编码RNA上重要位点化学修饰的修饰酶与调控因子。此外，我们也将利用上述新技术，探索化学修饰调控非编码RNA功能的过程与机制。

Analogous to DNA and histone modifications, post-transcriptional modifications have greatly expanded the function and structure of RNA molecules. Recently, the emerging field of “epitranscriptomics”, which focuses on chemical modifications to RNA, has attracted enormous attention from the RNA community. However, whether or not non-coding RNA of low abundance, in particular long non-coding RNAs (lncRNAs), also contains chemical modifications is largely unexplored. My group has recently developed two epitrancriptome sequencing technologies, which detects pseudouridine and 1-methyladenosine in the transcriptome-wide fashion. We discovered that these modifications are present in representative lncRNAs including MALAT1, NEAT1, XIST and etc. Based on our existing results, this proposal aims to develop new technologies for the transcriptome-wide detection of chemical modifications in lncRNAs. Meanwhile, we also plan to develop locus-specific methods for RNA modifications in lncRNA and identify key modification enzymes and regulatory factors. Finally, we will utilize these methods to explore the function and mechanism of RNA modifications within these lncRNAs.