Circular RNA circPIKfyve Acts as a Sponge of miR-21-3p To Enhance Antiviral Immunity through Regulation of MAVS in Teleost Fish

Circular RNAs (circRNAs) are a class of widespread and diverse covalently closed circular endogenous RNAs that exert crucial functions in regulating gene expression in mammals. However, the function and regulation mechanism of circRNAs in lower vertebrates are still unknown. Here, we discovered a novel circRNA derived from PIKfyve, named circPIKfyve, that is related to the antiviral responses in teleost fish. The results showed that circPIKfyve plays essential roles in host antiviral immunity and inhibition of SCRV replication. Moreover, we also found that the antiviral effect inhibited by miR-21-3p could be reversed with the addition of circPIKfyve. Our data revealed that circPIKfyve is a competitive endogenous RNA (ceRNA) of MAVS by sponging miR-21-3p, leading to the activation of the NF-kappa B/IRF3 pathway, which then enhanced the innate antiviral responses. In addition, we found that the RNA binding protein QKI is involved in the formation and regulation of circPIKfyve. Our results provide strong evidence that circRNAs play a regulatory role in antiviral immune responses in teleost fish. IMPORTANCE Here, we identified a novel circRNA, namely, circPIKfyve, that can act as a key regulator of the innate immune response in teleost fish. circPIKfyve acts as a molecular sponge by competitive adsorbing of miR-21-3p, thereby increasing the abundance of MAVS and activating the downstream NF-kappa B/IRF3 pathway to enhance the antiviral response. In addition, this study was the first to find that QKI protein is involved in regulating the formation of circPIKfyve in fish. The overall results of this study suggest that circPIKfyve plays an active regulatory role in the antiviral immune response of teleost fish.

Automated summary

In this study, a novel circRNA called circPIKfyve was identified as a key regulator of innate immune response in teleost fish, acting as a molecular sponge to competitively absorb miR-21-3p, thereby enhancing the antiviral response by increasing MAVS abundance and activating the downstream NF-kappa B/IRF3 pathway. Additionally, it was found for the first time that the RNA binding protein QKI is involved in regulating the formation of circPIKfyve in fish. These findings suggest that circPIKfyve plays a significant regulatory role in the antiviral immune response of teleost fish.