Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China;
J Immunol. 2022 Mar 1;208(5):1099-1114. doi: 10.4049/jimmunol.2100890. Epub 2022 Jan 31.
Circular RNA (circRNA) is produced by splicing head to tail and is widely distributed in multicellular organisms, and circRNA reportedly can participate in various cell biological processes. In this study, we discovered a novel exon-intron circRNA derived from probable E3 ubiquitin-protein ligase RNF217 () gene, namely, circRNF217, which was related to the antibacterial responses in teleost fish. Results indicated that circRNF217 played essential roles in host antibacterial immunity and inhibited the invasion into cells. Our study also found a microRNA miR-130-3p, which could inhibit antibacterial immune response and promote invasion into cells by targeting NOD1. Moreover, we also found that the antibacterial effect inhibited by miR-130-3p could be reversed with circRNF217. In mechanism, our data revealed that circRNF217 was a competing endogenous RNA of NOD1 by sponging miR-130-3p, leading to activation of the NF-κB pathway and then enhancing the innate antibacterial responses. In addition, we also found that circRNF217 can promote the antiviral response caused by rhabdovirus through targeting NOD1. Our study provides new insights for understanding the impact of circRNA on host-pathogen interactions and formulating fish disease prevention to resist the severely harmful infection.
环状 RNA（circRNA）通过头尾拼接产生，广泛分布于多细胞生物中，有报道称 circRNA 可参与多种细胞生物学过程。本研究发现了一种新型的exon-intron circRNA，来源于可能的 E3 泛素蛋白连接酶 RNF217（）基因，命名为 circRNF217，与硬骨鱼的抗菌反应有关。结果表明，circRNF217 在宿主抗菌免疫中发挥重要作用，抑制的入侵。本研究还发现了一种 microRNA miR-130-3p，它可以通过靶向 NOD1 抑制抗菌免疫反应并促进的入侵。此外，我们还发现 miR-130-3p 抑制的抗菌作用可以通过 circRNF217 逆转。在机制上，我们的数据表明 circRNF217 通过海绵 miR-130-3p 作为 NOD1 的竞争性内源性 RNA，激活 NF-κB 通路，从而增强先天抗菌反应。此外，我们还发现 circRNF217 可以通过靶向 NOD1 促进弹状病毒引起的抗病毒反应。本研究为理解 circRNA 对宿主-病原体相互作用的影响以及制定鱼类疾病预防措施以抵抗严重危害的感染提供了新的见解。
