细胞内RNA的动态修饰在生物体内发挥着重要的作用，相关研究正在成为生物学和医学领域研究热点之一。tRNA是细胞中参与蛋白质合成的重要分子之一。tRNA上的核苷酸存在广泛修饰，这些修饰对于稳定tRNA的三级结构以及tRNA在细胞内发挥功能起着重要作用。反密码子环是tRNA上修饰发生频率最高的地方，这些位点的修饰不仅会影响到翻译的精确性和效率，还可能参与到调控tRNA来源的tRF的生成。RNA:m5C甲基化修饰酶的基因表达异常与智力障碍等人类疾病密切相关。申请人实验室在tRNA以及tRNA甲基化修饰相关研究方面具有扎实的基础。本申请拟以催化tRNA反密码子环上特定位点的m5C修饰的两类m5C 甲基转移酶NSun3和Dnmt2为研究对象，研究其催化机理、对tRNA底物的识别机制和生物学功能。相关研究结果将为相关疾病的产生原因提供基础研究的依据。

Dynamic RNA modification plays important role in cellular processes, and relevant study represents an emerging research frontier in biology and medicine. tRNA is one of the important molecules which play central roles in protein synthesis. Nucleotides in tRNA are most post-transcriptionally modified, which generally reinforces the tertiary structure of tRNA and accelerate its cellular function. Nucleotides in anticodon loop are most often modified area in tRNA, these modifications are not only essential to the precise recognition and efficiency of protein translation, but also could modulate the production of functional tRNA fragments (tRF). The aberrant expression of RNA:m5C methyltransferase genes are closely related with many human diseases such as intellectual disability. Our lab has been working on tRNA and tRNA modification for decades and is very experienced in involved techniques. In this proposal, we plan to study the catalytic mechanism, RNA recognition and biological function of two RNA:m5C methyltransferases those are working on anticodon loop of tRNA, NSun3 and Dnmt2. Hopefully these research results will provide basic insights into understanding the causation of related disease.