circCBL and its host gene CBL collaboratively enhance the antiviral immunity and antibacterial immunity by targeting MITA in fish

Abstract

ABSTRACT circular RNAs (circRNAs) have been implicated in regulating various physiological and pathological processes, but their specific roles in antiviral and antibacterial immune responses require further investigation. In this study, the expression of circCBL was significantly increased in the Sininiperca chuatsi rhabdovirus (SCRV)-treated group and LPS-treated group of Miichthys miiuy , which may be related to the antiviral and antibacterial responses of teleost fish. The experimental results indicated that overexpression of circCBL can increase the production of antiviral genes and inflammatory factors, thereby promoting innate immunity against the invasion of SCRV and Vibrio anguillarum . Subsequent investigations have unveiled that circCBL plays a regulatory role in MITA through adsorbing miR-125a-1-3p, thereby facilitating the innate immune response. Remarkably, our findings suggested that the host gene CBL , which is associated with circCBL, also promotes the expression of MITA, consequently bolstering the antiviral and antibacterial immune responses. This discovery highlights the intricate interplay between circCBL and its host gene CBL , jointly governing the expression of MITA and ultimately amplifying the immune response against viral and bacterial infections. Overall, our research provides compelling experimental evidence corroborating the crucial regulatory functions of both circCBL and its host gene CBL in coordinating robust antiviral and antibacterial defense mechanisms. IMPORTANCE Increasing evidence indicates that circular RNAs exert crucial functions in regulating gene expression in mammals. However, the function of circRNAs in lower vertebrates still needs further exploration. Our research results demonstrated that circRNA, namely circCBL, is involved in modulating antiviral and antibacterial immune responses in lower vertebrates. In addition, our study also found that circCBL can serve as a competing endogenous RNA to facilitate MITA expression, thereby modulating MITA-mediated innate immunity. Further research has proved that the host gene CBL also promotes the expression of MITA, enhancing antiviral and antibacterial immune responses. Our study not only elucidated the underlying biological mechanism of the circRNA-miRNA-mRNA axis in the innate immune response of lower vertebrates but also unveiled the synergistic antibacterial and antiviral mechanisms between circRNA and its host gene in lower vertebrates.