RNA的转录后表观遗传修饰具有重要的生物学功能。转移核糖核酸(tRNA)是胞内转录后修饰最为密集的RNA分子，决定基因信息传递的速率与保真性。线粒体具有相对独立的蛋白质合成系统，对于正常细胞生命活动具有重要意义。人线粒体基因组编码22种线粒体tRNA，是线粒体翻译机器的核心分子之一。对于参与线粒体tRNA修饰的生物大分子的鉴定及修饰的分子机理知之甚少。影响线粒体tRNA修饰的tRNA或蛋白质基因突变造成多种线粒体相关疾病。例如，线粒体tRNA第34位5-牛磺酸甲基尿嘧啶核苷修饰(τm5U)缺陷导致线粒体脑肌病。本项目将聚焦于线粒体τm5U修饰及其潜在的修饰酶，阐释线粒体tRNA第34位τm5U修饰的分子机制及其修饰缺陷导致线粒体脑肌病的潜在机理。本项目有助于揭示线粒体tRNA转录后修饰的分子机制，阐释线粒体tRNA修饰缺陷导致疾病的分子机理，有望为相关疾病的诊治提供新视角、新靶点。

Post-transcriptional modification (PTM) of RNAs is of great biological significance. Transfer RNA (tRNA) undergoes most extensive post-transcriptional modifications in the cell, playing significant roles in rate and fidelity of genetic code decoding. Mitochondrion has its own protein synthesis machinery, determining normal cellular activities. Human mitochondrial genome encodes 22 mitochondrial tRNAs, being one of the most crucial components of mitochondria protein synthesis machinery. However, little is known about the modification enzymes and mechanisms of PTM of human mitochondrial tRNAs. Genetic mutations on mitochondrial tRNA genes or genes of tRNA modification enzymes lead to various mitochondrial disorders. For instance, defect in 5-taurinomethyl uridine modification at uridine 34 of various human mitochondrial tRNAs causes mitochondrial encephalomyopathies. This project will focus on mechanism of 5-taurinomethyl uridine modification and association between its defect with mitochondrial encephalomyopathies. It will help to reveal mechanism of PTM of human mitochondrial tRNAs, clarify the pathogenesis of defect in mitochondrial tRNA modification and provide potential insights into and targets for such mitochondrial diseases.