Antiviral type III CRISPR signalling via conjugation of ATP and SAM.
Antiviral type III CRISPR signalling via conjugation of ATP and SAM.
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DOI：
10.1038/s41586-023-06620-5
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发表时间：
2023-10
期刊：
影响因子：
64.8
通讯作者：
White, Malcolm F.
中科院分区：
文献类型：
--
作者：
Chi, Haotian;Hoikkala, Ville;Gruschow, Sabine;Graham, Shirley;Shirran, Sally;White, Malcolm F.
CRISPR系统在原核世界中广泛存在，提供针对移动的遗传元件的适应性免疫。具有特征基因cas 10的III型CRISPR系统使用CRISPR RNA来检测非自身RNA，激活酶促Cas 10亚基以直接地（经由整合的组氨酸-天冬氨酸（HD）核酸酶结构域）或间接地（经由环状寡腺苷酸第二信使的合成以激活多种辅助效应物）防御细胞对抗移动的遗传元件。III型CRISPR系统的一个子集编码未表征的CorA家族膜蛋白和相关的NrN家族磷酸二酯酶，其被预测在抗病毒防御中起作用。在这里，我们证明了来自脆弱拟杆菌的CorA相关III-B型（Cmr）CRISPR系统在大肠杆菌中表达时提供了针对移动的遗传元件的免疫力。然而，B。fragilis Cmr在活化时不合成环状寡腺苷酸物质，而是通过磷酸二酯键将ATP缀合至SAM而产生S-腺苷甲硫氨酸（SAM）-AMP（SAM也称为腺苷甲硫氨酸）。一旦合成，SAM-AMP与CorA效应物结合，可能通过破坏膜完整性导致细胞休眠或死亡。SAM-AMP被CRISPR相关的磷酸二酯酶或SAM-AMP裂解酶降解，可能提供类似于环状寡腺苷酸特异性环核酸酶的“关闭开关”。因此，SAM-AMP代表了一类新的抗病毒信号传导的第二信使，其可能在不同的细胞环境中发挥不同的作用。脆弱拟杆菌III型CRISPR蛋白Cmr将ATP与S-腺苷甲硫氨酸结合，产生S-腺苷甲硫氨酸（SAM）-AMP，这是一种在抗病毒信号传导中起作用的新型第二信使。
CRISPR systems are widespread in the prokaryotic world, providing adaptive immunity against mobile genetic elements. Type III CRISPR systems, with the signature gene cas10, use CRISPR RNA to detect non-self RNA, activating the enzymatic Cas10 subunit to defend the cell against mobile genetic elements either directly, via the integral histidine–aspartate (HD) nuclease domain or indirectly, via synthesis of cyclic oligoadenylate second messengers to activate diverse ancillary effectors. A subset of type III CRISPR systems encode an uncharacterized CorA-family membrane protein and an associated NrN family phosphodiesterase that are predicted to function in antiviral defence. Here we demonstrate that the CorA-associated type III-B (Cmr) CRISPR system from Bacteroides fragilis provides immunity against mobile genetic elements when expressed in Escherichia coli. However, B. fragilis Cmr does not synthesize cyclic oligoadenylate species on activation, instead generating S-adenosyl methionine (SAM)-AMP (SAM is also known as AdoMet) by conjugating ATP to SAM via a phosphodiester bond. Once synthesized, SAM-AMP binds to the CorA effector, presumably leading to cell dormancy or death by disruption of the membrane integrity. SAM-AMP is degraded by CRISPR-associated phosphodiesterases or a SAM-AMP lyase, potentially providing an ‘off switch’ analogous to cyclic oligoadenylate-specific ring nucleases. SAM-AMP thus represents a new class of second messenger for antiviral signalling, which may function in different roles in diverse cellular contexts. The Bacteroides fragilis type III CRISPR protein Cmr conjugates ATP to S-adenosyl methionine, generating S-adenosyl methionine (SAM)-AMP, a novel second messenger with a role in antiviral signalling.
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影响因子：
3.7
作者：
Russel, Jakob;Pinilla-Redondo, Rafael;Sorensen, Soren J.
通讯作者：
Sorensen, Soren J.
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1261/rna.078739.121
发表时间：
2021-05-13
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Athukoralage JS;White MF
通讯作者：
White MF
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
10.5
作者：
Elmore JR;Sheppard NF;Ramia N;Deighan T;Li H;Terns RM;Terns MP
通讯作者：
Terns MP