Chu Qing, Xu Tianjun, Zheng Weiwei, Chang Renjie, Zhang Lei
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China.
Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.
Sci China Life Sci. 2021 Jul;64(7):1131-1148. doi: 10.1007/s11427-020-1789-5. Epub 2020 Sep 24.
Viral infection induces the initiation of antiviral effectors and cytokines which are critical mediators of innate antiviral responses. The critical molecular determinants are responsible for triggering an appropriate immune response. Long noncoding RNAs (lncRNAs) have emerged as new gene modulators involved in various biological processes, while how lncRNAs operate in lower vertebrates are still unknown. Here, we discover a long noncoding RNA, termed antiviral-associated long noncoding RNA (AANCR), as a novel regulator for innate antiviral responses in teleost fish. The results indicate that fish MITA plays an essential role in host antiviral responses and inhibition of Siniperca chuatsi rhabdovirus (SCRV) production. miR-210 reduces MITA expression and suppress MITA-mediated antiviral responses, which may help viruses evade host antiviral responses. Further, AANCR functions as a competing endogenous RNA (ceRNA) for miR-210 to control protein abundance of MITA, thereby inhibiting SCRV replication and promoting antiviral responses. Our data not only shed new light on understanding the function role of lncRNA in biological processes in teleost fish, but confirmed the hypothesis that ceRNA networks exist widely in vertebrates.
病毒感染会引发抗病毒效应分子和细胞因子的产生，这些是先天性抗病毒反应的关键介质。关键分子决定因素负责触发适当的免疫反应。长链非编码RNA（lncRNAs）已成为参与各种生物过程的新型基因调节剂，而lncRNAs在低等脊椎动物中如何发挥作用仍不清楚。在这里，我们发现了一种长链非编码RNA，称为抗病毒相关长链非编码RNA（AANCR），它是硬骨鱼先天性抗病毒反应的新型调节剂。结果表明，鱼类MITA在宿主抗病毒反应和抑制鳜鱼弹状病毒（SCRV）产生中起重要作用。miR-210降低MITA表达并抑制MITA介导的抗病毒反应，这可能有助于病毒逃避宿主抗病毒反应。此外，AANCR作为miR-210的竞争性内源RNA（ceRNA）来控制MITA的蛋白质丰度，从而抑制SCRV复制并促进抗病毒反应。我们的数据不仅为理解lncRNA在硬骨鱼生物过程中的功能作用提供了新线索，还证实了ceRNA网络在脊椎动物中广泛存在的假设。
