昆虫RNA编辑模式及其在系统进化中的功能研究

RNA editing is one of the most important mechanisms of post transcription regulation. By substituting the nucleotide sequence of mRNA, RNA editing changes the amino acid of protein and affects the function of biological system. According to pervious report, RNA editing plays an important role in tissue development, which might be related to the incidence of neural system disorder and associated with adaptation evolution in extreme environment. Because of the complexity of RNA editing mechanism and the difficulty in experimental verification, the identification of RNA editing target and function analysis lack of efficient methods and theories. Currently, RNA editing research mainly focused on higher animals; while for insect species it is still in the initial stage. To understand the evolution and function of insect RNA editing is critical to study the evolution of transcription regulation and the association study of RNA editing and phenotype in other species. Based on high-throughput sequencing data, we aimed to identify RNA editing targets in Drosophila with a comprehensive method. Besides, with gene family evolution study, the role of RNA editing in long time evolution will be discussed. In the aspect of gene transcription regulation, we will illustrate the influence of RNA editing in regulation networks. This project will construct theoretical system and technological method for RNA editing targets identification, annotation pipeline, evolutionary study and function analysis.

RNA编辑是一种重要的转录后调控机制，通过对mRNA上核苷酸的改变来影响蛋白质翻译的产物，进而影响整个生物系统的功能。研究表明，RNA编辑在组织发育的过程中起重要作用，可能与神经系统发育病变相关，还与物种如何适应环境变化有密切的关系。 由于RNA编辑机制的复杂性和实验验证的困难，对RNA编辑靶位点的鉴定和进化功能分析始终缺乏高效而准确的方法和理论。RNA编辑的研究目前集中在高等动物中，昆虫中RNA编辑研究尚处于起步阶段。了解昆虫RNA编辑机制的进化和功能，对认识生物体调控系统进化规律有重要作用，为研究RNA编辑和表型的关联奠定基础。本课题拟以高通量测序数据为基础，结合多层次数据，对果蝇的RNA编辑机制进行系统化分析。结合基因家族进化分析，阐述RNA编辑在长期进化选择中扮演的角色；从转录调控网络角度探索其在生物学功能。希望建立一套系统化鉴定、注释、分析RNA编辑靶位点的理论体系和技术方法。

作为重要的转录后调控机制之一，RNA编辑具有诱导产生不同功能的蛋白质的重要特点。本研究鉴定获得了目前最完整的果蝇属（覆盖7个果蝇物种）中存在的RNA编辑事件。本研究总计鉴定到2734个果蝇基因上存在的9281个RNA编辑事件（55.5%位于编码区）。根据进化特征，RNA编辑事情可以分为三类：（1）偶发于singleton gene的RNA编辑（2）存在于（跨物种）多基因家族，但编辑位点不保守的RNA编辑事件（3）存在于（跨物种）多基因家族，且编辑位点保守的RNA编辑事件。此三类RNA编辑事件具有显著不同的进化特征。其中，跨物种保守的RNA编辑事件主要集中于影响神经系统的信号通路。我们进一步阐述了在发育和交配过程中RNA编辑的动态变化等特征。