RNA编辑影响RNA二级结构介导可变剪接的调控机制研究

我们通过RNA补偿突变表明以非编码RNA二级结构基础的联合机制在14-3-3ξ, Dscam等基因的互斥可变剪接中的指导作用(Yang等, Nat Struct Mol Biol, 2011)。有趣的是，我们发现有些RNA二级结构发生A至I RNA编辑，从而影响RNA配对竞争而导致剪接体的比例发生改变。在此基础上，通过缺失和补偿突变技术，进一步分析A至I RNA编辑影响RNA二级结构竞争效应的动态，应用ADAR-/ADAR-突变体、RNAi和过度表达技术，深入分析RNA编辑对互斥可变剪接及相关性状的调控作用，探明A至I RNA编辑影响互斥剪接的分子机制，对从多层次阐明RNA二级结构介导的可变剪接调控具有重要意义。

Mutation-based rescue experiments indicate that combined mechanism based on the non-coding RNA secondary structure to direct the mutually exclusive splicing events occur in genes like 14-3-3ξ, Dscam and so on (Yang et al, Nat Struct Mol Biol, 2011). More interestingly, A-to-I RNA editing event was also identified in some of these RNA secondary structures; therefore it may affect the pairing pattern of the particular RNA duplex to achieve more spliced variants within the cell in a spatial and temporal manner. Based on this finding, by deletion and compensatory mutations, we will further investigate the mechanism how A-to-I RNA editing to direct novel RNA secondary structure formation. With the help of ADAR-/ADAR- mutant, RNAi and overexpression analysis, it would be much easier to understand the molecular mechanism of A-to-I RNA editing that affect mutually exclusive splicing events. It would be of great significance to clarify the regulatory mechanism of RNA secondary structure-mediated alternative splicing.