Bacterial cGAS senses a viral RNA to initiate immunity

Dalton V. Banh, Cameron G. Roberts, Adrian Morales-Amador, Brandon A. Berryhill, Waqas Chaudhry, Bruce R. Levin, Sean F. Brady and Luciano A. Marraffini ()
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Dalton V. Banh: The Rockefeller University
Cameron G. Roberts: The Rockefeller University
Adrian Morales-Amador: The Rockefeller University
Brandon A. Berryhill: Department of Biology, Emory University
Waqas Chaudhry: Department of Biology, Emory University
Bruce R. Levin: Department of Biology, Emory University
Sean F. Brady: The Rockefeller University
Luciano A. Marraffini: The Rockefeller University

Nature, 2023, vol. 623, issue 7989, 1001-1008

Abstract: Abstract Cyclic oligonucleotide-based antiphage signalling systems (CBASS) protect prokaryotes from viral (phage) attack through the production of cyclic oligonucleotides, which activate effector proteins that trigger the death of the infected host1,2. How bacterial cyclases recognize phage infection is not known. Here we show that staphylococcal phages produce a structured RNA transcribed from the terminase subunit genes, termed CBASS-activating bacteriophage RNA (cabRNA), which binds to a positively charged surface of the CdnE03 cyclase and promotes the synthesis of the cyclic dinucleotide cGAMP to activate the CBASS immune response. Phages that escape the CBASS defence harbour mutations that lead to the generation of a longer form of the cabRNA that cannot activate CdnE03. Since mammalian oligoadenylate synthetases also bind viral double-stranded RNA during the interferon response, our results reveal a conserved mechanism for the activation of innate antiviral defence pathways.

Date: 2023
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DOI: 10.1038/s41586-023-06743-9

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