Long noncoding RNA MIR2187HG suppresses TBK1-mediated antiviral signaling through deriving miR-2187-3p in teleost fish.
2021
Long non-coding RNAs (lncRNAs) function as microregulatory factors that influence gene expression after a variety of pathogenic infection, which have been extensively studied in the past few years. Although less attention has been paid to lncRNAs in lower vertebrates than in mammals, current studies reveals that lncRNAs plays a vital role in fish stimulated by pathogens. Here, we discovered a new lncRNA, termed as MIR2187HG, which can function as a precursor of a small RNA miR-2187-3p with regulatory functions in miiuy croaker (Miichthys miiuy). Upon Siniperca chuatsi rhabdovirus (SCRV) virus infection, the expression levels of MIR2187HG were remarkably enhanced. Elevated MIR2187HG expression can act as a pivotally negative regulator that participates in the innate immune response of teleost fish to inhibit the intracellular TANK-binding kinase 1 (TBK1)-mediated antiviral signaling pathways, which can effectively avoid excessive immunity. In addition, we found that the SCRV virus could also utilize MIR2187HG to enhance its own number. Our results not only provide evidence regarding the involvement of the lncRNAs in response to anti-viruses in fish, but also broaden our understanding of the function of lncRNAs as precursor miRNA in teleost fish for the first time. Importance: SCRV infection upregulates MIR2187HG levels, which in turn suppresses SCRV-triggered type I interferon production, thus promoting viral replication in miiuy croaker. Notably, MIR2187HG regulates the release of miR-2187-3p, and TBK1 is a target of miR-2187-3p. MIR2187HG could obtain the function from miR-2187-3p to inhibit TBK1 expression and subsequently modulate TBK1-mediated NF-κB and IRF3 signaling. The collective results suggest that the novel regulation mechanism of TBK1-mediated antiviral response during RNA viral infection was regulated by MIR2187HG. Therefore, a new regulation mechanism for lncRNAs to regulate antiviral immune responses in fish is proposed.
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