SARM suppresses TRIF, TRAF3, and IRF3/7 mediated antiviral signaling in large yellow croaker .

As a TIR domain-containing molecular, sterile α-and armadillo motif-containing protein (SARM) acts as an adaptor in Toll-like receptor (TLR) signaling, and also plays important roles in mediating apoptosis and neuronal injury. In the present study, the ortholog of , named as , was cloned and identified in large yellow croaker (). The full-length ORF of consists of 2,154 bp, encoding a protein of 717 amino acids (aa), which is comprised of an N-terminal ARM domain, two SAM domains, and a C-terminal TIR domain. Confocal microscopy revealed that -SARM was mainly distributed in the cytoplasm, and the mRNA expression level of was broadly distributed in all the detected organs/tissues, with the highest expression level found in the brain. The expression patterns of could be induced in response to poly I:C, LPS, PGN stimulations, and infection. Notably, although the overexpression of -SARM could significantly induce NF-κB, IRF3, IRF7, and type I IFN promoter activation, whereas the co-expression of SARM with TRIF, -TRAF3, -IRF3, or -IRF7 significantly down-regulated the induction of NF-κB, IRF3, IRF7, or type I IFN promoter activation, and suppressed the antiviral effects as well as the downstream antiviral-related genes expression compared to the only overexpression of -TRIF, -TRAF3, -IRF3, or -IRF7. Co-immunoprecipitation (Co-IP) assays also demonstrated that SARM interacts separately with -TRIF, -TRAF3, -IRF3, and -IRF7. It is thus collectively suggested that -SARM functions as a negative regulator in -TRIF, -TRAF3, and -IRF3/7 involved antiviral signaling.