转移核糖核酸（tRNA）是细胞翻译机器的关键分子, 含有较多的修饰成分。tRNA修饰可从不同的方面影响细胞蛋白质合成，并且与人类疾病发生密切相关，但是对人类tRNA修饰生成机制及其生物学功能的了解依然相当匮乏。我们前期研究在人类基因组中鉴定了大量的功能未知的孤儿snoRNA，在此基础上，本项目拟采用计算与实验相结合的方法研究“孤儿”snoRNA的功能，从中发现和鉴定与tRNA有相互作用的向导snoRNA，解析这些snoRNA介导tRNA 2`-O-核糖甲基化修饰的新机制，进一步考察由snoRNA介导的tRNA核糖甲基化对细胞生理生化及表型的影响，阐明真核生物tRNA 核糖甲基化修饰由非编码RNA介导的遗传新机制及其生物学意义。

Transfer RNAs (tRNAs)，the key molecules to the cell "translation machine", contain many chemical modifications. These modifications impacts protein synthesis in cells, and closely related to human disease. However, there are still a lot of challenging problems in the biogenesis mechanism and biological function of the RNA modifications. In our preliminary study, we have identified a large number of orphan snoRNAs with unknown function. On this basis, the project intends to use a combination of computational and experimental methods to study the function of the orphan snoRNAs. Discovering and identifying the orphan snoRNAs interacting with tRNAs; deciphering the new mechanism underlying snoRNA mediated ribose methylation of tRNAs; further investigating the effects of snoRNA-mediated methylation on cell physiology and biochemistry and phenotype. This study will shed insight into the new genetic mechanism of the methylation biogenesis of eukaryotic tRNAs and the biological significance of the methylation mediated by non-coding RNAs.