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

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.

The long noncoding RNA MIR122HG is a precursor for miR-122-5p and negatively regulates the TAK1-induced innate immune response in teleost fish

“…The mechanism of competing endogenous RNA is one of the most studied hotspots, revealing that lncRNA slows down the inhibitory effect of mRNA by competitively binding miRNA. This mechanism was revealed in fish studies, and our previous research shows that antiviral-associated lncRNA ( 41 ), MAVS antiviral-related lncRNA ( 33 ), and IRL ( 42 ) act as molecular sponges to bind miRNAs and slow down the adverse consequences caused by excessive miRNA suppression of the immune response. In addition, lncRNA can be used as the host gene of miRNA to regulate the production of miRNA to indirectly regulate mRNA.…”

The circular RNA circBCL2L1 regulates innate immune responses via microRNA-mediated downregulation of TRAF6 in teleost fish

“…Moreover, it has been reported that the regulation mechanism that long ncRNA NARL can competitive adsorption miR-217-5p to regulate the miR-217-5p/NOD1 axis is widespread in teleost fish (36). lncRNA IRL can competitively adsorb miRNA to regulate the miR-27c-3p/IRAK4 axis that is widespread in teleost fish (54). In addition, we found a lncRNA J o u r n a l P r e -p r o o f 10 MARL in teleost fish, which can target and regulate MAVS mediated antiviral immune response through competitive adsorption of miR-122 (55).…”

microRNA-210 and microRNA-3570 Negatively Regulate NF-κB-Mediated Inflammatory Responses by Targeting RIPK2 in Teleost Fish

“…Therefore, in our study, to avoid nonspecific effects of excessive accumulation of this high molecular weight RNA species on target gene expression, we prolonged the transfection time with miRNA mimics and to study the effect of miRNA on target genes. In teleost fish, many researches have shown that endogenous regulatory molecules miRNAs can regulate the immune response by regulating crucial immune-related genes, such as MITA, IRAK4, TBK1 (54)(55)(56). However, there are few reports on the regulation of RIPK2 by miRNAs.…”