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长非编码 RNA IRL 通过抑制 miR-27c-3p 依赖的 IRAK4 下调来调节 NF-κB 介导的免疫反应在硬骨鱼中。

Long noncoding RNA IRL regulates NF-κB-mediated immune responses through suppression of miR-27c-3p-dependent IRAK4 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.

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.

出版信息

J Biol Chem. 2021 Jan-Jun;296:100304. doi: 10.1016/j.jbc.2021.100304. Epub 2021 Jan 16.

Abstract

Growing pieces of evidence show that the long noncoding RNAs (lncRNAs) as new regulators participate in the regulation of various physiological and pathological processes. The study of lncRNA in lower invertebrates is still unclear compared with that in mammals. Here, we identified a novel lncRNA, termed IRAK4-related lncRNA (IRL), as a key regulator for innate immunity in teleost fish. We find that miR-27c-3p inhibits IRAK4 expression and thus weakens the NF-κB-mediated signaling pathway. Furthermore, the Gram-negative bacterium Vibrio anguillarum and lipopolysaccharide significantly upregulated host lncRNA IRL expression. Results indicate that IRL functions as a competing endogenous RNA for miR-27c-3p to regulate protein abundance of IRAK4; thus, invading microorganisms are eliminated and immune responses are promoted. Our study also demonstrates the regulation mechanism that lncRNA IRL can competitively adsorb miRNA to regulate the miR-27c-3p/IRAK4 axis that is widespread in teleost fish.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)作为新的调控因子参与了各种生理和病理过程的调控。与哺乳动物相比,低等无脊椎动物中 lncRNA 的研究尚不清楚。在这里,我们鉴定了一个新的 lncRNA,称为 IRAK4 相关 lncRNA(IRL),它是硬骨鱼类先天免疫的关键调节因子。我们发现 miR-27c-3p 抑制 IRAK4 的表达,从而减弱 NF-κB 介导的信号通路。此外,革兰氏阴性菌鳗弧菌和脂多糖显著上调了宿主 lncRNA IRL 的表达。结果表明,IRL 作为 miR-27c-3p 的竞争性内源性 RNA 发挥作用,调节 IRAK4 的蛋白丰度;从而消灭入侵的微生物并促进免疫反应。我们的研究还表明,lncRNA IRL 可以通过竞争性吸附 miRNA 来调节 miR-27c-3p/IRAK4 轴的调控机制,这种机制在硬骨鱼类中广泛存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a79d/7949060/e7d1e4629afb/gr1.jpg

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