tRNA是生命体内一类必需的非编码RNA，其经典功能是参与蛋白质合成。最近，人们发现tRNA及其来源的片段还具有重要的非蛋白质合成的功能，能够参与调控多种生理病理过程，tRNA也因此再次成为明星分子，在生物医学领域被广泛关注。tRNA是含修饰最密集的RNA分子之一，tRNA的修饰被发现与神经疾病、代谢综合征及癌症等一系列人类疾病密切相关。包括m1A在内的一些tRNA修饰水平在体内呈动态变化，随着环境，如：氧化压力、UV损伤和营养等的变化而变化。高等真核生物的线粒体tRNA的第九位存在保守的m1A修饰(m1A9)，具有重要的生物学功能。本申请拟以线粒体tRNA:m1A9修饰的甲基转移酶（Trm10C）及去甲基化酶(AlkbH1) 和相关tRNA底物分子作为研究对象，拟阐明该动态修饰对tRNA的结构、代谢和功能的影响，特别是对线粒体蛋白质合成的影响；同时研究外界环境改变对该修饰的调控机理。

tRNA is a class of essential noncoding RNA, and its classical function is involved in protein synthesis. Recently, tRNA and tRNA derived fragments have been found to play regulatory roles beyond protein synthesis in many physiological and pathological processes. Thus, tRNA once again becomes a star molecule in the field of biomedicine. Among cellular RNAs, tRNA is one with heaviest modifications, and tRNA modifications have been found to be closely related with many human diseases such as neurological diseases, metabolic disorders, and cancers. The level of some tRNA modifications （e.g. m1A） is dynamic in vivo, which could respond to environmental changes such as oxidative stress, UV damage, and culture conditions. A conservative m1A modification is happened on site 9 (m1A9) of mitochondrial tRNAs in higher eukaryotes, and this modification plays important roles. In this proposal, we plan to study this tRNA:m1A9 modification by using the related modification enzyme (Trm10C), demodification enzyme (AlkbH1), and tRNA substrates as research objectives, trying to elucidate the role of this m1A9 modification in the structure, dynamics, and function of tRNAs, especially its role in mitochondrial protein synthesis；Meanwhile, we will investigate the modulation mechanism of this dynamic tRNA modification by environmental changes.