长链非编码RNA调控果蝇运动能力的分子机制研究

The functional exploration of long non-coding RNAs (lncRNAs) is becoming the heat point of present biological studies. Increasing evidences suggest that the development and function of the neural system mainly relied on RNA editing and the intricate spatiotemporal expression of lncRNAs, which may provide the clue to investigate the multi-tiered relationship between neural development and function and neurological diseases. Using bioinformatics, one lncRNA（nc7） expressed in Drosophila neural system was predicted and its exact expression was confirmed by molecular biological method. The full sequence of nc7 was obtained by 5' and 3' RACE and Northern blotting. Elementary work demonstrated the expression level of the adjacent movement-related protein-coding gene,nicotinic acetylcholine receptor(nAchR) was changed by nc7-overexpression in Drosophila S2 cell. We suppose nc7 could participate in the neural regulation on movement. In this project, the expression pattern of nc7 through the whole development stages will be detected by in situ hybridization. And, we will examine the effects of nc7 on the movement ability by constructing the RNA interference line, deficiency line and overexpression line of nc7. Furthermore, we will explore the molecular mechanism underlying the regulation on movement ablility by nc7. The accomplishment of this project will enrich ncRNAs' biological significance and provide insights for exploring the pathogenesis of neurological diseases associated with movement disorders.

对于长链非编码RNA（lncRNA）功能的探究成为日益关注的科学问题，神经系统的发育和功能很可能依赖于lncRNAs调节网络，对这些网络的干扰可能引起多种神经性疾病。我们通过生物信息预测了某个在果蝇神经系统中表达的lncRNA（nc7），并验证其在神经系统有表达。并通过5'和3'RACE结合Northern 得到nc7的全长序列。初步功能试验提示，在果蝇S2细胞中过表达nc7，影响了与果蝇运动相关基因烟碱型乙酰胆碱受体（nAchR）的表达。因此我们假设nc7参与果蝇神经系统对运动的调节。本项目中，将通过原位杂交检测nc7在不同发育时期的表达模式；构建nc7的RNA沉默、缺失以及过表达品系来检测nc7在调控果蝇运动能力中的作用；通过分子生物学方法探讨nc7参与调控果蝇运动能力的分子机制。本项目的完成将进一步丰富ncRNA的生物学功能，并为探索伴有运动异常的神经性疾病的发病机制提供一定参考

对于长链非编码RNA（long non-coding RNA, lncRNA）功能的探索成为日益关注的科学问题，神经系统的发育和功能很可能依赖于lncRNA的调节网络，对这些网络的干扰可能引起多种神经性疾病。我们针对一些长链非编码RNA进行了研究：阐明了某一果蝇长链非编码RNA的分子特征及其对邻近编码基因的调控作用；针对果蝇长链非编码RNA在神经系统中的作用进行了综述；采用基因芯片对人腹主动脉瘤组织中的长链非编码RNA进行了筛选，得到了有明显变化的候选长链非编码RNA，进一步采用定量RT-PCR进行了验证得到了一致的结果，并研究了候选长链非编码RNA对腹主动脉瘤相关编码基因的调控作用。 这些研究结果进一步丰富了长链非编码RNA的生物学功能，并为后续深入研究长链非编码RNA参与疾病的病理机制提供一定的参考。