Bacterial cGAS senses a viral RNA to initiate immunity.

Bacterial cGAS senses a viral RNA to initiate immunity.
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DOI:
10.1038/s41586-023-06743-9
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发表时间:
2023-11
期刊:
影响因子:
64.8
通讯作者:
Marraffini, Luciano A.
Marraffini, Luciano A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Banh, Dalton V.;Roberts, Cameron G.;Morales-Amador, Adrian;Berryhill, Brandon A.;Chaudhry, Waqas;Levin, Bruce R.;Brady, Sean F.;Marraffini, Luciano A.

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基于环状寡核苷酸的抗噬菌体信号系统(CBASS)通过产生环状寡核苷酸来保护原核生物免受病毒(噬菌体)的攻击,环状寡核苷酸激活效应蛋白,触发被感染宿主的死亡。细菌环化酶如何识别噬菌体感染尚不清楚。本研究表明,葡萄球菌噬菌体产生一种由末端酶亚基基因转录而成的结构化RNA,称为CBASS激活噬菌体RNA (cabRNA),它与CdnE03环化酶的正电荷表面结合,促进环二核苷酸cGAMP的合成,从而激活CBASS免疫反应。逃避CBASS防御的噬菌体携带突变,导致产生不能激活CdnE03的较长形式的cabRNA。由于哺乳动物低聚腺苷酸合成酶也在干扰素应答过程中结合病毒双链RNA,我们的研究结果揭示了激活先天抗病毒防御途径的保守机制。葡萄球菌CdnE03环化酶识别葡萄球菌噬菌体产生的结构化RNA分子,触发环状寡核苷酸的产生,从而导致细菌细胞死亡——这是一种跨生命域保守的抗病毒防御机制。
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 host. 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. Staphylococcus CdnE03 cyclase recognizes structured RNA molecules produced by staphylococcal phages, triggering cyclic oligonucleotide production and, thereby, bacterial cell death—a mechanism of antiviral defence conserved across domains of life.
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