Growing numbers of studies have shown that circular RNAs (circRNAs) can function as regulatory factors to regulate the innate immune response, cell proliferation, cell migration, and other important processes in mammals. However, the function and regulatory mechanism of circRNAs in lower vertebrates are still unclear. Here, we discovered a novel circRNA derived from the gene encoding Bcl-2-like protein 1 (BCL2L1) gene, named circBCL2L1, which was related to the innate immune responses in teleost fish. Results indicated that circBCL2L1 played essential roles in host antiviral immunity and antibacterial immunity. Our study also identified a microRNA, miR-30c-3-3p, which could inhibit the innate immune response by targeting inflammatory mediator TRAF6. And TRAF6 is a key signal transduction factor in innate immune response mediated by TLRs. Moreover, we also found that the antiviral and antibacterial effects inhibited by miR-30c-3-3p could be reversed with the expression of circBCL2L1. Our data revealed that circBCL2L1 functioned as a competing endogenous RNA (ceRNA) of TRAF6 by competing for binding with miR-30c-3-3p, leading to activation of the NF-κB/IRF3 inflammatory pathway and then enhancing the innate immune responses. Our results suggest that circRNAs can play an important role in the innate immune response of teleost fish.

中文翻译：

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环状 RNA circBCL2L1 通过 microRNA 介导的硬骨鱼 TRAF6 下调来调节先天免疫反应。

越来越多的研究表明，环状RNA（circRNA）可以作为调节因子来调节哺乳动物的先天免疫反应、细胞增殖、细胞迁移和其他重要过程。然而，circRNA在低等脊椎动物中的功能和调控机制仍不清楚。在这里，我们发现了一种源自编码Bcl-2样蛋白1（BCL2L1）基因的新型circRNA，命名为circBCL2L1，它与硬骨鱼的先天免疫反应有关。结果表明，circBCL2L1在宿主抗病毒免疫和抗菌免疫中发挥重要作用。我们的研究还发现了一种 microRNA，miR-30c-3-3p，它可以通过靶向炎症介质 TRAF6 来抑制先天免疫反应。TRAF6是TLR介导的先天免疫反应中的关键信号转导因子。此外，我们还发现miR-30c-3-3p抑制的抗病毒和抗菌作用可以随着circBCL2L1的表达而逆转。我们的数据显示，circBCL2L1 通过与 miR-30c-3-3p 竞争结合，充当 TRAF6 的竞争性内源 RNA (ceRNA)，从而激活 NF-κB/IRF3 炎症通路，然后增强先天免疫反应。我们的结果表明，circRNA 在硬骨鱼的先天免疫反应中发挥着重要作用。