中文摘要
可变剪接是产生蛋白质和功能多样性的重要途径,互斥剪接是一种有趣且严格调控的可变剪接方式,可产生数目惊人的蛋白异构体,如黑腹果蝇Dscam 基因通过互斥剪接产生多达38 016种的异构体蛋白质,但其发生调控和遗传机制还不太清楚。我们前期研究揭示了以RNA二级结构为基础的联合机制在互斥可变剪接中的指导作用(Nat Struct Mol Biol, 2011; Nat Commun, 2012)。最近对Yel等基因研究获得了更为激动人心的发现,并提出了新的调控模型假说并获得初步证实。在此基础上,结合全基因组比较基因组保守进化分析和高通量RNA结构测序技术鉴定介导RNA互斥剪接的二级结构,并采用多物种在多个基因上通过实验证明新模型及其适用性;探明RNA二级结构是如何与蛋白相互作用从而启动外显子的剪接,最终建立多停泊位点的RNA竞争匹配控制互斥剪接的新模型。
英文摘要
Alternative splicing is an important means to increase protein repertoire. Mutually exclusive splicing is a strictly regulatory and interesting alternative splicing; for example, Drosophila melanogaster Dscam (Down syndrome cell adhesion molecule) gene potentially produces 38 016 different mRNA and protein isoforms. However, the regulatory mechanisms remain obscure. Our previoud study indicates that RNA structures ensure only-one variant exon selection by the spliceosome (Nat Struct Mol Biol, 2011; Nat Commun, 2012). Recently, we discove very exciting arrangement of intronic elements and then propose a novel model, which was confirmed by some data. Next, we identy genome-wide RNA structures in mutually exclusive splicing by comparative genome analyses and high-through structure sequencing, and confirmed the model in more genes from various species. In addition, trans-acting factors which contribute to this splicing process will be revealed. Our ultimate aim is to imply a novel mechanism to ensure mutually exclusive splicing.
