细胞内RNA的动态甲基化修饰研究正在成为生物学和医学领域研究热点之一。RNA: m5C是一种广泛存在的RNA修饰。NSun甲基化酶家族是真核生物中主要的RNA:m5C修饰酶，由七个成员组成，其中多个成员的基因突变被发现与智力障碍、男性不育及癌症等人类疾病密切相关。然而，由于缺乏三级结构信息，NSun家族成员的RNA底物识别机制以及RNA:m5C的催化机制均不清楚。与此同时，RNA: m5C的生物学功能也有待阐明。人NSun6于2015年被鉴定出来的，是催化tRNA氨基酸接受茎上第72位m5C修饰的甲基化酶。随后，我们鉴定出tRNA被NSun6识别的元件，并揭示了NSun6是tRNA专一性的修饰酶。本项目拟通过生物化学和结构生物学等方法去阐明NSun6的催化机制及识别tRNA的方式;同时用细胞生物学手段对NSun6及其催化的tRNA:m5C 修饰的生物学功能进行初步探索。

Study of dynamic cellular RNA modifications represents an emerging research frontier in biology and medicine. RNA:m5C methylation is a common chemical modification widely happened in cellular RNAs. NSun methyltransferase family is the main RNA m5C modification enzymes in eukaryotes, which is composed of seven members. The genetic mutations of several NSun family members have been reported to be closely involved in many human diseases such as intellectual disability, male infertility and cancers. Due to lack of structural information, the RNA recognition mode and RNA:m5C modification mechanism of NSuns remain unclear for a long time. Meanwhile, the biological functions of RNA:m5C modification remained to be explored. In 2015, human NSun6 was identified as the methyltransferase catalyzing the m5C72 modification at the amino acid acceptor of many tRNAs. We subsequently reported the tRNA recognition elements by NSun6 and reveal that NSun6 is a tRNA specific methyltransferse. In this proposal, we plan to study the catalytic mechanism and RNA recognition mode of NSun6 by biochemical and structural studies. In the meantime, the biological function of NSun6 and the RNA:m5C modification it introduced will also be investigated through cell biological methods.