microRNA-489 negatively modulates RIG-I signaling pathway via targeting TRAF6 in miiuy croaker after poly(I:C)...

The innate immune response is first line of host defense against pathogen invasion. However, excessive activation of immune responses may cause autoimmune diseases and excessive inflammation. Retinoic acid-inducible gene I (RIG-I) is an important cytoplasmic pathogen recognition receptor that is activated on virus infection. TNF-receptor-associated factor 6 (TRAF6) plays an essential role in the RIG-I-mediated signaling pathway. MicroRNAs (miRNAs) are noncoding RNAs that are emerging as important regulators of immune responses. In this study, we found that the overexpression of miR-489 mimics and pre-miR-489 significantly suppressed the luciferase activity of the wild-type TRAF6 3'UTR, whereas mutant-type led to a complete abrogation of the negative effect. In addition, we also observed that miR-489 can negatively regulate TRAF6 at the level of translation. More importantly, we demonstrated that miR-489 is a negative regulator of TRAF6 involved in the immune response to poly(I:C) stimulation. These common findings indicated that miR-489 plays a regulatory role in host-virus interactions by targeting TRAF6. Overall, all of the present results provide direct evidence that miR-489 is involved in the regulation of TRAF6 expression in miiuy croaker, which will help to better understand the complex regulatory networks of teleost fish.