RNA-binding protein Roq modulates the Drosophila STING antiviral immune response

The STING (stimulator of interferon genes) signaling pathway plays a pivotal role in the immune defense against viral infections in a wide range of vertebrates and invertebrates. However, the regulatory picture of this pathway is still incomplete. Herein, we investigate the involvement of Roq (Roquin), a typical RNA-binding protein, in modulating the Drosophila melanogaster (fruit fly) STING antiviral innate immunity. We show that Roq harbors a negative impact on the STING signaling pathway in a manner depending on its ROQ and CBM (CAF40-binding motif) domains. Importantly, viral infection induces the STING/NF-kB signaling-dependent expression of Roq, which forms a functional ribonuclease complex with CCR4/NOT for the deadenylation and degradation of Sting mRNA. Silencing of the Roq/CCR4/NOT axis leads to an excessive STING signaling upon viral infection. Collectively, our study sheds light on a feedback regulatory loop involving Roq-CCR4-NOT-Sting in the contribution to the fly antiviral immune defense. • RNA-binding protein Roq modulates the host antiviral immune response in Drosophila. • Drosophila Roq directly binds to Sting mRNA in a domain-dependent manner. • Drosophila Roq forms a functional complex with CCR4/Not1 to mediate the deadenylation and degradation of Sting mRNA.