LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppressing pol-miR-n199-3p-mediated SARM downregulation in Paralichthys olivaceus

LncRNAs (long non-coding RNAs) have been recognized as key modulators in mammalian immunity, and particular emphasis is placed on the mechanism of lncRNA-mediated ceRNA (competitive endogenous RNA) crosstalk. To date, investigations on lncRNAs in lower vertebrates still remain tentative. In the present study, we characterized the first immune-related lncRNA, termed pol-lnc78, in teleost fish Japanese flounder (Paralichthys olivaceus). We found that pol-lnc78 acts as a ceRNA for pol-miR-n199-3p to SARM (sterile alpha and armadillo motif-containing protein), the last discovered TIR adaptor. This intertwined ceRNA trinity regulates flounder antibacterial responses through TLR signaling pathway. Specifically, SARM as a negative regulator exacerbates bacterial infection through inhibiting the expression of inflammatory cytokines IL-1β and TNF-α. Pol-miR-n199-3p reduces SARM expression via specific interacting with the 3’UTR region, thereby promoting SARM-dependent inflammatory cytokines expression and protecting host against bacterial dissemination. Furthermore, pol-lnc78 sponges pol-miR-n199-3p to relieve the expression inhibition on SARM. In particular, during infection, the negative regulators pol-lnc78 and SARM are significantly downregulated, while pol-miR-n199-3p is significantly upregulated in expression, thus favoring host antibacterial defense. The results of this study provide new insights into the mechanism of fish immunity, and open up new horizons to a better understanding of ceRNA crosstalk in lower vertebrates.