RNA 5mC甲基转移酶复合物的鉴定和功能研究

项目名称： RNA 5mC甲基转移酶复合物的鉴定和功能研究

项目编号： No.31500659

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 杨莹

作者单位： 中国科学院北京基因组研究所

项目金额： 20万元

中文摘要： RNA具有调控和信息分子的双重功能，其中mRNA编码蛋白质。mRNA加工代谢机制包括了转录、剪接、转运、定位、质控等，受到顺式和反式元件及RNA化学修饰的调控，而RNA修饰如何调控mRNA加工代谢是近来RNA生物学研究的重大科学问题，关键是鉴定出RNA化学修饰的转移酶复合物及其功能。我们前期研究发现了一种mRNA广泛存在的甲基化修饰5mC的甲基转移酶催化亚基NSUN2，建立了RNA 5mC重亚硫酸盐-高通量测序技术及生物信息分析方法，初步鉴定了mRNA的5mC分布规律及NSUN2结合的RNA，发现了NSUN2调控脂肪前体细胞分化的重要功能。本项目拟整合分子细胞、生化，化学生物学、基因组和生物信息学交叉技术，重点鉴定RNA 5mC甲基转移酶复合物，阐明5mC修饰调控mRNA选择性剪接和翻译的机理，为RNA甲基化修饰调控mRNA加工和代谢提供新的理论依据。

中文关键词： RNA修饰；5-甲基胞嘧啶；甲基转移酶；选择性剪接；翻译

英文摘要： RNAs function as regulatory and signaling molecules, amid which mRNAs encode proteins. The processing and metabolism of mRNAs including transcription, splicing, transport, localization and quality control, is regulated by cis- and trans- elements as well as certain types of chemical modifications on RNA. How RNA modifications modulate mRNA processing and metabolism is the most prevalent and significant scientific question in RNA biology, whereby, the key is to identify the methyltransferase complex of specific modifications and their functions. In our pioneering studies, we identified one methyltransferase component of the extensively spread 5mC methylation on mRNA, NSUN2; established the RNA 5mC bisulfite high-throughput sequencing technology as well as bioinformatics analysis procedures; unveiled distribution characteristics of mRNA 5mC and RNA species-associated with NSUN2; and found a regulatory role of NSUN2 in pre-adipocytes differentiation. By integrating multiple technologies ranging from molecular cell biology, biochemistry, chemical biology, to genomics and bioinformatics, we aim to identify the RNA 5mC methyltransferase complex and explore molecular mechanisms how RNA 5mC regulates mRNA alternative splicing and translation, by then illustrate biological significance of RNA methylations controlling mRNA processing and metabolism.

英文关键词： RNA modification;5-methylcytosine (5mC);Methyltransferase;Alternative splicing;Translation