TRAF5 splicing variants associate with TRAF3 and RIP1 in NF-κB and type I IFN signaling in large yellow croaker Larimichthys crocea.

As a member of the tumor necrosis factor receptor-associated factor (TRAF) family, TRAF5 acts as a crucial adaptor molecule and plays important roles in the host innate immune responses. In the present study, the typical form and a splicing variant of TRAF5, termed Lc-TRAF5_tv1 and Lc-TRAF5_tv2 were characterized in large yellow croaker (Larimichthys crocea). The putative Lc -TRAF5_tv1 protein is constituted of 577 aa, contains a RING finger domain, two zinc finger domains, a coiled-coil domain, and a MATH domain, whereas Lc -TRAF5_tv2 protein is constituted of 236 aa and only contains a RING finger domain due to a premature stop resulted from the intron retention. Subcellular localization analysis revealed that both of Lc -TRAF5_tv1 and Lc -TRAF5_tv2 were localized in the cytoplasm, with Lc -TRAF5_tv2 found to aggregate around the nucleus. It was revealed that Lc-TRAF5_tv1 mRNA was broadly expressed in examined organs/tissues and showed extremely higher level than that of Lc-TRAF5_tv2 , and both of them could be up-regulated under poly I:C, LPS, PGN, and Pseudomonas plecoglossicida stimulations in vivo. Interestingly, overexpression of Lc -TRAF5_tv1 and Lc -TRAF5_tv2 could significantly induce NF-κB but not IFN1 activation, whereas co-expression of them remarkably induced IFN1 activation but impaired NF-κB activation. In addition, both Lc -TRAF5_tv1 and Lc -TRAF5_tv2 were associated with TRAF3 and RIP1 in IFN1 activation, whereas only Lc -TRAF5_tv1 cooperated with TRAF3 and RIP1 in NF-κB activation. These results collectively indicated that the splicing variant together with the typical form of TRAF5 function importantly in the regulation of host immune signaling in teleosts. • A novel TRAF5 splicing variant Lc -TRAF5_tv2 was characterized in vertebrates. • Lc-TRAF5_tv1 and Lc-TRAF5_tv2 can be induced by both viral and bacterial PAMPs. • Lc -TRAF5_tv2 cooperates with Lc -TRAF5_tv1 in type I IFN activation. • Lc -TRAF5_tv1 associates with TRAF3 and RIP1 in NF-κB and type I IFN activation. • Lc -TRAF5_tv2 associates with TRAF3 and RIP1 in type I IFN activation. [ABSTRACT FROM AUTHOR]