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.
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; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai, China.
J Biol Chem. 2021 Jan-Jun;296:100414. doi: 10.1016/j.jbc.2021.100414. Epub 2021 Feb 11.
Increasing evidence shows that the long noncoding RNA (lncRNA) is a major regulator and participates in the regulation of various physiological and pathological processes, such as cell proliferation, differentiation, metastasis, and apoptosis. Unlike mammals, however, the study of lncRNA in lower invertebrates is just beginning and the extent of lncRNA-mediate regulation remains unclear. Here, we for the first time identify an lncRNA, termed nucleotide oligomerization domain 1 (NOD1) antibacterial and antiviral-related lncRNA (NARL), as a key regulator for innate immunity in teleost fish. We found that NOD1 plays an important role in the antibacterial and antiviral process in fish and that the microRNA miR-217-5p inhibits NOD1 expression and thus weakens the NF-κB and the IRF3-driven signaling pathway. Furthermore, our results indicated that NARL functions as a competing endogenous RNA (ceRNA) for miR-217-5p to regulate protein abundance of NOD1; thus, invading microorganisms are eliminated and immune responses are promoted. Our study also demonstrates the regulation mechanism that lncRNA NARL can competitive adsorption miR-217-5p to regulate the miR-217-5p/NOD1 axis is widespread in teleost fish. Taken together, our results reveal that NARL in fish is a critical positive regulator of innate immune responses to viral and bacterial infection by suppressing a feedback to NOD1-NF-κB/IRF3-mediated signaling.
越来越多的证据表明，长非编码 RNA（lncRNA）是主要的调控因子，并参与调节各种生理和病理过程，如细胞增殖、分化、转移和凋亡。然而，与哺乳动物不同，对低等无脊椎动物中 lncRNA 的研究才刚刚开始，lncRNA 介导的调节程度尚不清楚。在这里，我们首次鉴定了一种 lncRNA，称为核苷酸寡聚化结构域 1（NOD1）抗菌和抗病毒相关 lncRNA（NARL），作为硬骨鱼类先天免疫的关键调节因子。我们发现 NOD1 在鱼类的抗菌和抗病毒过程中起着重要作用，microRNA miR-217-5p 抑制 NOD1 的表达，从而削弱 NF-κB 和 IRF3 驱动的信号通路。此外，我们的结果表明，NARL 作为 miR-217-5p 的竞争性内源 RNA（ceRNA）发挥作用，调节 NOD1 的蛋白丰度；因此，入侵的微生物被消除，免疫反应得到促进。我们的研究还表明，lncRNA NARL 可以竞争性吸附 miR-217-5p 来调节 miR-217-5p/NOD1 轴的调节机制在硬骨鱼类中广泛存在。总之，我们的结果表明，鱼类中的 NARL 通过抑制 NOD1-NF-κB/IRF3 介导的信号的反馈来抑制先天免疫反应，是对病毒和细菌感染的先天免疫反应的关键正调控因子。
