线粒体16S rRNA甲基转移酶以及相关蛋白质调控线粒体核糖体组装的分子机制的结构与功能研究

线粒体作为细胞生命活动的能量来源，与人类健康，衰老，疾病息息相关。2'-O-核糖甲基化修饰是哺乳动物线粒体16S rRNA上常见的修饰。RNA甲基转移酶MRM1，MRM2以及RNMTL1分别负责16S rRNA上G1145，U1369和G1370的甲基化，稳定16S rRNA，促进线粒体大亚基的装配，完成肽基转移酶反应和tRNA识别。这些特异性的识别及催化对于线粒体核糖体的装配起到了至关重要的作用，然而其中的分子机制和结构基础还是未知的。.本项目拟以甲基转移酶MRM1，MRM2以及RNMTL1为研究对象，利用结构生物学、生物化学和细胞生物学方法，解析其与16S rRNA复合物晶体结构，阐明其识别修饰16S rRNA的功能，揭示其对于线粒体核糖体组装影响的分子机制，为线粒体相关疾病的治疗提供理论支持。

As essential molecular machinery for the maintenance of cellular energy, mitochondria are closely related to human health, aging and diseases. 2'-O-ribose methylation is the most common modification found on mammalian mitochondrial 16S rRNA. RNA methyltransferases MRM1, MRM2, and RNMTL1 are responsible for the 2'-O-ribose methylation of G1145, U1369 and G1370 on 16S rRNA, respectively. These 2'-O-ribose methylations play vital roles in maintaining the 16S rRNA stability and promoting the assembly of the large mitochondrial subunits, which are responsible for the peptidyl transferase reaction and tRNA recognition. The specific recognition and catalysis of the above methylations are indispensable for the assembly of mitochondrial ribosomes. However, the molecular mechanism and structural basis between these RNA methyltransferases and 16S rRNA still remain unknown..In this project, we intend to focus on the methyltransferase MRM1, MRM2 and RNMTL1, analyze the crystal structures of their complexes with 16s rRNA by means of structural biology, biochemistry and cell biology, clarify their functions of recognizing and modifying 16s rRNA, and reveal the molecular mechanisms of mitochondrial ribosome assembly, so as to provide theoretical support for the treatment of mitochondrial related diseases.