A conserved miR-7132a/SOCS1/STAT2 regulatory axis enhances type I IFN antiviral responses in teleost fish

Type I interferon (IFN) signaling plays an essential role in restricting viral infection. Accumulating evidence indicates that microRNAs (miRNAs) serve as key regulators of the type I IFN signaling in mammals. However, whether the miRNA-mediated regulation is involved in type I IFN signaling in teleost fish remains unknown. In large yellow croaker (Larimichthys crocea, Lc), we found that miR-7132a induced by poly(I: C) or type I IFN LcIFNi promotes type I IFN responses in vitro and in vivo. Mechanistically, miR-7132a directly targets the 3'UTR of LcSOCS1 and inhibits LcSOCS1 expression by reducing its mRNA stability and repressing its protein translation. LcSOCS1 promotes K48-linked polyubiquitination at K382 residue of LcSTAT2 via its E3 ubiquitin ligase activity, leading to proteasomal degradation of LcSTAT2. By reducing LcSOCS1-mediated degradation of LcSTAT2, miR-7132a promotes LcSTAT2-dependent type I IFN antiviral responses. Notably, miR-7132a-mediated inhibition of SOCS1 is also present in other teleost species. Collectively, these findings reveal a novel positive regulatory axis by which miR-7132a promotes type I IFN antiviral responses by suppressing SOCS1-mediated STAT2 degradation. Thus, this study provides valuable insights into miRNA-mediated regulatory axis of type I IFN responses in teleost fish.