miR-927通过激活Hippo信号通路调控果蝇翅膀发育的分子机制探究

Long distance migration of winged insects is a key and difficult point for agricultural pest prevention. Therefore, studying the molecular mechanism of insect wing development and finding ways to inhibit the development of insect wings is of great theoretical significance and practical value for pest prevention. Hippo signaling pathway governs the development of insect wings though promoting cell apoptosis and inhibiting cell proliferation. Unfortunately, how to modulate the homeostasis of the Hippo pathway is still unclear. Through genetic screening, we found that overexpression of miR-927 in Drosophila melanogaster resulted in a small wing, accompanying with ectopic activation of the Hippo signaling pathway. Further bioinformatics and biochemical analysis indicated that the co-transcription factor Yki in the Hippo pathway is a potential target for miR-927. Based on this, we speculate that miR-927 activates the Hippo signaling pathway by inhibiting the expression of Yki, culminating in regulating the development of wings. On this basis, this project intends to analyze the molecular mechanism of miR-927 activating Hippo signaling pathway, and clarify the important role of miR-927 in the process of wing development. The research will provide important data to perfect the regulation of Hippo signaling pathway, and also provide a new theoretical basis for studying the development of insect wings and pest prevention.

有翅目昆虫的远距离迁徙是农业害虫防治的重点和难点，因此，探究昆虫翅膀发育的分子机制，寻找抑制昆虫翅膀发育的方法，对害虫的防治具有重大的理论意义和实用价值。Hippo信号通路促进细胞凋亡、抑制细胞增殖，进而调控昆虫翅膀的发育。遗憾的是，对Hippo通路稳态的调控仍然知之甚少。通过遗传筛选，我们发现在黑腹果蝇中过表达miR-927导致翅膀面积变小，且异常激活Hippo信号通路。进一步的生物信息学和生化分析表明Hippo通路中的辅助转录因子Yki是miR-927潜在靶点。基于此，我们推测miR-927通过抑制Yki表达，激活Hippo信号通路，最终调控黑腹果蝇翅膀发育。本项目拟在此基础上，深入解析miR-927激活Hippo信号通路的分子机理，以期阐明miR-927在翅膀发育中的重要作用。该研究将为完善Hippo信号通路的调控提供重要数据，也对研究昆虫翅发育及害虫防治提供了新的理论基础。

翅是昆虫重要的器官，赋予了昆虫飞行能力，加快了昆虫演化。探究翅发育的分子机制，不仅有助于了解昆虫演化和物种多样性，也有利于农业害虫的防治。小分子RNA（miRNA）通过和特定靶基因mRNA的3’-UTR结合，抑制靶基因的翻译。MiRNA参与几乎所有的细胞生物学过程，但是其在昆虫翅发育中的重要作用，尚不清楚。申请者前期通过高通量遗传筛选，鉴定到miR-927调控果蝇翅发育。在本项目资助下，申请人取得以下研究结果：1、过表达miR-927显著减小翅面积；2、抑制miR-927微弱增加翅面积；3、miR-927可诱发细胞凋亡；4、miR-927抑制Hippo信号通路靶基因表达；5、遗传学分析发现miR-927作用于Yki；6、miR-927与yki mRNA 3’-UTR结合，促进yki mRNA降解。本项目揭示了miR-927通过靶向yki mRNA，减小果蝇翅面积，拓展了对Yki转录后水平调控的认识。在项目资助下，发表SCI论文6篇，授权国家发明专利1项。