近年来的转录组数据揭示了生物体中存在大量的反义长链非编码RNA(lncRNA), 但大多数反义lncRNA的功能和作用机制并不清楚。果蝇Dscam1(唐氏综合症细胞黏附分子)基因通过可变剪接方式可产生38,016种同源异构体；最近，我们鉴定了果蝇Dscam1基因位点的反义lncRNA Dscam1AS，并通过实验分析表明其可调控Dscam1基因可变剪接。在此基础上，本项目结合CRISPR/Cas9编辑技术和高通量RNA测序技术揭示Dscam1AS表达与Dscam1可变外显子选择的相关性，阐明反义lncRNA Dscam1AS调控Dscam1可变剪接的具体机制，探明反义lncRNA Dscam1AS在神经发育等生理过程中的重要作用。该研究不仅对lncRNA功能和可变剪接的调控机制研究提供了新的思路，并且为神经性等疾病治疗药物提供了潜在靶标。

Recent transcriptome analysis reveal a vast repertoire of antisense long noncoding RNAs (lncRNA), however, their roles and the underlying molecular mechanisms remain largely unclear. D. melanogaster Dscam1 encodes 38,016 distinct isoforms via alternative splicing; we have recently identified an antisense lncRNA at the Drosophila Dscam1 locus, Dscam1AS, and experimental analysis indicates that Dscam1AS could regulate Dscam1 alternative splicing. Next, combining CRISPR/Cas9 technology with high high-throughput sequencing approach, we will explore the relation between Dscam1AS expression and the inclusion of Dscam1 alternative exon; and will elucidate the mechanism how antisense lncRNA Dscam1AS regulates the selection of alternative exons of Dscam1. We will propose a novel model for the regulation of lncRNA Dscam1AS in Dscam1 alternative splicing. Additionally, we will reveal the biological roles of the Dscam1AS, particularly in nervous system development. The study will not only provides the new idea for the biological function of lncRNA and regulation of alternative splicing, but also provides the potential therapeutic target for some diseases.