微小核糖核酸是一类细胞内源性的小分子非编码核糖核酸，在正常生理以及病理活动过程中发挥着重要的调控作用。已有研究发现微小核糖核酸自身存在众多不同的化学修饰，然而对于这些带有化学修饰的微小核糖核酸所具有的生理病理意义仍然知之甚少。本项目拟在已有的研究基础上针对肌苷修饰微小核糖核酸的生物学功能开展化学生物学研究，筛选与癌症等重大疾病相关且在成熟体中带有肌苷修饰的微小核糖核酸作为研究对象，通过在肌苷修饰前、后微小核糖核酸的末端引入不同生物正交官能团构建功能探针分子，并结合相应生物正交反应等化学生物学研究方法对肌苷修饰前、后微小核糖核酸所结合的靶基因进行分别的标记、富集、分离和鉴定。基于对微小核糖核酸靶基因的鉴定，我们将进一步揭示肌苷修饰前、后微小核糖核酸在生理病理过程中通过调节这些靶基因所发挥的不同生物学功能，从而阐明肌苷化学修饰对于微小核糖核酸生理病理意义的影响。

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs, which play pivotal roles in physiological and pathological processes. Previous studies have shown that miRNAs can be endogenously modified with different chemical groups. However, little is known about the biological significance of miRNAs with different chemical modifications. Here, we propose to dissect the biological function of inosine-modified miRNAs in details. We will screen candidate miRNAs that are closely related with cancer development and modified with inosine through deep-sequencing. By construction of chemical probes for normal miRNAs and inosine-modified miRNAs through modifying them with different bio-orthogonal groups, we will label these miRNAs and associated targets by using corresponding bio-orthogonal chemistries. Furthermore, we will isolate and identify these target genes through high-throughput sequencing. Moreover, we will further dissect the biological function of both normal miRNAs and inosine-modified miRNAs, and the biological significance of inosine modifications will also be revealed.