RNA:浙江大学金勇丰实验室阐明RNA互斥剪接调控机制
近日，国际著名期刊《RNA》上在线发表浙江大学生命科学学院金勇丰实验室阐明RNA互斥剪接调控机制研究文章，博士生岳媛和博士后杨赟为共同第一作者，金勇丰教授为论文通讯作者。
黑腹果蝇Dscam基因通过互斥可变剪接产生多达38 016种的异构体蛋白质，在许多教科书和专著中被用作经典案例予以描述。本研究发现在昆虫Srp基因中复制外显子簇中存在特异顺式元件和进化保守的双向RNA二级结构，突变实验表明，上游的停泊位点能特异性启动最下游的外显子，下游的停泊位点能特异性启动最上游的外显子，他们之间具有竞争关系;可变外显子的选择不仅与RNA配对互补强度呈正相关;并且该模型更好地解释了2个外显子簇任意扩展到几十个外显子簇的互斥可变剪接。重要的是，我们在膜翅目等昆虫Dscam外显子4、9等基因中也发现并证实了类似的进化保守的双向RNA二级结构，表明是普遍存在介导RNA互斥可变剪接的机制。
原文链接：
Long-range RNA pairings contribute to mutually exclusive splicing
原文摘要：
Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of theDscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA–RNA interactions in gene regulatory networks.
作者：金勇丰
