从酵母SUA5到人YRDC基因高度保守，科学家从结构上推测其具有重要功能，有高度优先研究的价值。酵母的同源基因SUA5通过影响tRNA的t6A修饰而影响了蛋白翻译，同时通过调节端粒复制的活性而影响了端粒长度的维持。我们前期研究发现：通过病毒感染小鼠肝脏降低YRDC表达后，肝脏tRNA的t6A修饰水平显著降低，肝脏脂肪蓄积；长期高脂饮食进一步加剧了脂肪肝病变，并出现肝纤维化和肝肿瘤病变趋势。本项目拟通过小鼠肝脏敲减和高表达YRDC的小鼠模型，通过Microarray表达谱基因芯片和质谱蛋白测序以及免疫共沉淀等方法，从脂质代谢各个环节研究YRDC参与脂质平衡的具体分子机制；通过建立小鼠脂肪肝和脂肪肝诱导肝癌的疾病模型，研究YRDC在这些疾病的发生发展和预后中的作用和分子机制；同时初步探讨人体YRDC的功能性多态位点，以及其与临床肝脏脂肪病变的相关性，为临床预防和治疗这类疾病提供新思路和新靶点。

YRDC is highly conserved among three kingdoms of life, and based on the structure and domains, YRDC has been speculated to have very important roles in physiology and pathology and merits a priority of investigation. SUA5, YRDC homolog in yeast, has been found to play the following roles in yeast: 1, SUA5 is responsible for t6A modification in tRNA, which affects the rate and fidelity of protein translation; 2, SUA5 regulates the activity of telomere replication and maintains the telomere length. In our previous studies, we observed that down-regulated YRDC expression in liver decreased the level of t6A modification in tRNA; that the mouse with YRDC knockdown in liver showed higher lipid accumulation compared to the control mouse with normal level of YRDC; that high fat diet to mouse further aggravated the progress from hepatosteatosis to hepatofibrosis and hepatocellular carcinoma. This project aims to investigate the mechanism of how YRDC participate in liver lipid metabolism, and further to explore the roles of YRDC in fatty liver disease models, which eventually will provide the new concept and new target for prevention and treatment of these diseases.