可逆化学修饰调控 lncRNA二级结构机制及其功能研究

The regulations and functions of lncRNAs in transcription, translation and epigenetics and their roles in cell growth and differentiation and development have attracted more and more research interests. However, much of the current research mainly focuses on phenotypic description and genetic perturbation with gene knockdown, knockout and overexpression. The study of the molecular mechanism has remained very limited due to the lack of appropriate approaches and techniques. In our pioneering studies, we have established high-throughput techniques to measure RNA secondary structures and chemical modifications. The primary sequences, structures and reversible modifications of lncRNA, and in particular their interplays, are essential to the understanding of their working mechanisms. We propose to develop new high-throughput experimental techniques and computational methods for the study of lncRNA structures and modifications, by combining multi-disciplinary approaches from cell and molecular biology and bioinformatics. With these enabling techniques, we will identify and study functional secondary structural elements, modifications, and their relationships. We will focus on their dynamic changes under stress conditions and conservations in evolution. This project will provide new ideas and techniques for the broad research of lncRNA biology.

lncRNA 参与转录、翻译及表观遗传等多个水平的调控过程，在细胞的生长及分化、组织器官的发育等过程中起重要作用；其调控和功能得到越来越多的重视。然而目前大部分研究只停留于对lncRNA表面生物学现象的描述，对其功能的研究大多是采取基因敲低、敲除和过表达等细胞和遗传学手段。由于研究手段的缺乏，对lncRNA作用的分子机制了解相当有限。我们在前期工作中建立了一套RNA二级结构和化学修饰检测和信息分析技术，为从RNA序列，结构和化学修饰三个层次之间的相互关系角度揭示lncRNA行使功能机制提供了扎实基础。本项目通过整合多学科交叉优势，结合二级结构和化学修饰高通量测序，细胞和分子生物学、生物信息学等，发展新的高通量实验技术和计算方法，来研究lncRNA的结构与修饰的机制及其功能，研究二级结构元件和修饰的关系，及其在应激条件下和进化中动态性和保守性，为lncRNA研究领域提供新思路和技术手段。

lncRNA 参与转录、翻译及表观遗传等多个水平的调控过程，在细胞的生长及分化、组织器官的发育等过程中起重要作用；其调控和功能得到越来越多的重视。然而目前大部分研究只停留于对lncRNA表面生物学现象的描述，对其功能的研究大多是采取基因敲低、敲除和过表达等细胞和遗传学手段。由于研究手段的缺乏，对lncRNA作用的分子机制了解相当有限。我们在前期工作中建立了一套RNA二级结构和化学修饰检测和信息分析技术，为从RNA序列，结构和化学修饰三个层次之间的相互关系角度揭示lncRNA行使功能机制提供了扎实基础。本项目通过整合多学科交叉优势，结合二级结构和化学修饰高通量测序，细胞和分子生物学、生物信息学等，发展新的高通量实验技术和计算方法，来研究lncRNA的结构与修饰的机制及其功能，研究二级结构元件和修饰的关系，及其在应激条件下和进化中动态性和保守性，为lncRNA研究领域提供新思路和技术手段。