鮸鱼长链非编码RNA MRL调控MyD88介导的抗细菌信号通路的分子机制

海水养殖鱼类的细菌性疾病给养殖产业造成了严重损失，目前主流的抗生素治疗方式会导致耐药菌株的出现并增加食物安全风险，基于基因免疫疗法的生物防控策略可以提高机体自身免疫力进而增强抗病力，而前提是首先需要发现能够增加鱼类机体免疫力的免疫增强子。申请人前期筛选出一个在哈维氏弧菌感染后的鮸鱼中高表达的长链非编码RNA（lncRNA）并命名为MRL，过表达和敲降后能分别促进和抑制炎症细胞因子的表达，通过RIP技术鉴定出MRL可以与miRNA调控元件AGO2结合，说明MRL可能作为ceRNA参与了miRNA的调控过程，进一步发现MRL可以正调控TLR抗细菌通路中接头分子MyD88的表达，推测lncRNA MRL与miRNA竞争性互作共同调控MyD88介导的抗细菌通路。本项目旨在阐明MRL调控鱼类抗细菌通路的分子机制，揭示鮸鱼病害的防控及鱼类免疫调控机理，为鱼类的疾病防控及健康养殖奠定理论基础。

Bacterial diseases of mariculture fish have caused serious losses to the aquaculture industry. The current mainstream antibiotic treatment methods have led to the emergence of drug-resistant strains and increased food safety risks. Biological prevention and control strategies based on gene immunotherapy can improve the body’s own immunity. To enhance disease resistance, the prerequisite is to find immune enhancers that can increase the immunity of fish. The applicant previously screened a long non-coding RNA (lncRNA), named MRL, which was highly expressed in Miichthys miiuy infected with Vibrio harveyi. Overexpression or knockdown of lncRNA MRL can promote or inhibit the expression of inflammatory cytokines, respectively. The RIP experiment showed that MRL can bind to the miRNA regulatory element AGO2, indicating that MRL may serves as a ceRNA for miRNA. Furthermore, it was found that MRL can positively regulate the expression of MyD88 in the TLR antibacterial pathway. It is speculated that lncRNA MRL can act as a competing endogenous RNA of miRNA to regulate the antibacterial pathway mediated by MyD88. This project aims to clarify the molecular mechanism of lncRNA MRL regulating fish anti-bacterial pathways, reveal the prevention of fish diseases and the molecular mechanism of fish immunity, and lay a theoretical foundation for fish disease prevention and control and healthy breeding.