Bacterial cGAS senses a viral RNA to initiate immunity
CBASS immunity protects prokaryotes from viral (phage) attack through the production of cyclic dinucleotides which activate effector proteins that trigger the death of the infected host. How bacterial cyclases recognize phage infection is not known. Here we show that staphylococcal phages produce a highly structured 400-nt RNA, termed CBASS-activating bacteriophage RNA (cabRNA), that binds to a positively charged surface of the CdnE03 cyclase and promotes the synthesis of the cyclic dinucleotide cGAMP. Phages that escape CBASS immunity harbor mutations that lead to the generation of a longer form of the cabRNA that cannot activate CdnE03. Since the mammalian cyclase OAS1 also binds viral dsRNA during the interferon response, our results reveal a conserved mechanism for the activation of innate antiviral defense pathways.