Nanjing Normal University College of Marine Science and Engineering
Nanjing Normal University, College of Marine Science and Engineering, 2 Xuelin Road, Nanjing, Jiangsu
This work was supported by the grants of National Natural Science Foundation of China (42006082), Natural Science Foundation of Jiangsu Province of China (BK20221323), the “JBGS” Project of Seed Industry Revitalization in Jiangsu Province (JBGS  034), and State Key Laboratory of Developmental Biology of Freshwater Fish (2021KF009).
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.