环状 RNA circDtx1 通过抑制 miR-15a-5p 依赖的 TRIF 下调来调节 IRF3 介导的抗病毒免疫反应。

Circular RNA circDtx1 regulates IRF3-mediated antiviral immune responses through suppression of miR-15a-5p-dependent TRIF downregulation in teleost fish.

机构信息

Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.

Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.

出版信息

PLoS Pathog. 2021 Mar 18;17(3):e1009438. doi: 10.1371/journal.ppat.1009438. eCollection 2021 Mar.

Circular RNAs (circRNAs) represent a class of widespread and diverse covalently closed circular endogenous RNAs that exert crucial functions in regulating gene expression in mammals. However, the function and regulation mechanism of circRNAs in lower vertebrates are still unknown. Here, we discovered a novel circRNA derived from Deltex E3 ubiquitin ligase 1 (Dtx1) gene, namely, circDtx1, which was related to the antiviral responses in teleost fish. Results indicated that circDtx1 played essential roles in host antiviral immunity and inhibition of SCRV replication. Our study also found a microRNA miR-15a-5p, which could inhibit antiviral immune response and promote viral replication by targeting TRIF. Moreover, we also found that the antiviral effect inhibited by miR-15a-5p could be reversed with the circDtx1. In mechanism, our data revealed that circDtx1 was a competing endogenous RNA (ceRNA) of TRIF by sponging miR-15a-5p, leading to activation of the NF-κB/IRF3 pathway, and then enhancing the innate antiviral responses. Our results indicated that circRNAs played a regulatory role in immune responses in teleost fish.

环状 RNA（circRNAs）是一类广泛存在且多样化的共价闭合环状内源性 RNA，在哺乳动物中对基因表达的调控起着至关重要的作用。然而，circRNAs 在低等脊椎动物中的功能和调控机制尚不清楚。在这里，我们发现了一种源自 Deltex E3 泛素连接酶 1（Dtx1）基因的新型环状 RNA，即 circDtx1，它与鱼类的抗病毒反应有关。结果表明，circDtx1 在宿主抗病毒免疫和抑制 SCRV 复制中发挥着重要作用。我们的研究还发现了一种 microRNA miR-15a-5p，它可以通过靶向 TRIF 抑制抗病毒免疫反应并促进病毒复制。此外，我们还发现 miR-15a-5p 的抗病毒作用可以被 circDtx1 逆转。在机制上，我们的数据表明 circDtx1 是 TRIF 的竞争性内源 RNA（ceRNA），通过海绵吸附 miR-15a-5p，激活 NF-κB/IRF3 通路，从而增强先天抗病毒反应。我们的结果表明，circRNAs 在鱼类的免疫反应中发挥了调节作用。