Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic oligoadenylate.

Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic oligoadenylate.
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DOI:
10.1038/s41586-018-0557-5
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发表时间:
2018-10
期刊:
影响因子:
64.8
通讯作者:
White MF
White MF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Athukoralage JS;Rouillon C;Graham S;Grüschow S;White MF

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CRISPR系统利用小的CRISPR rna指导效应复合物降解入侵的核酸,为原核生物提供针对移动遗传元件的适应性免疫。III型效应复合物最近被证明可以在结合靶RNA上合成一种新的第二信使环寡腺苷酸(cOA)。反过来,辅酶a通过CARF (CRISPR相关的罗斯曼折叠)结构域结合并激活核糖核酸酶和其他因子,在细胞中诱导对免疫很重要的抗病毒状态。重置系统的“关闭开关”的机制尚不清楚。在这里,我们报告的核酸酶降解这些辅酶a环分子的鉴定。“环核酸酶”本身是一种具有金属独立机制的CARF家族蛋白,它切割cA4环产生线性二腺苷酸物种并关闭抗病毒状态。环状核酸酶的鉴定为CRISPR系统增加了重要的见解。
The CRISPR system provides adaptive immunity against mobile genetic elements in prokaryotes, utilising small CRISPR RNAs which direct effector complexes to degrade invading nucleic acids. Type III effector complexes were recently demonstrated to synthesise a novel second messenger, cyclic oligoadenylate (cOA), on binding target RNA. cOA in turn binds to and activates ribonucleases and other factors via a CARF (CRISPR associated Rossman Fold) domain, inducing an antiviral state in the cell that is important for immunity. The mechanism of the “off-switch” that resets the system is not understood. Here, we report the identification of the nuclease that degrades these cOA ring molecules. The “Ring nuclease” is itself a CARF family protein with a metal independent mechanism, which cleaves cA4 rings to generate linear di-adenylate species and switches off the antiviral state. The identification of Ring nucleases adds an important insight to the CRISPR system.
DOI: 10.1083/jcb.201004104
发表时间: 2010-05-31
期刊: The Journal of cell biology
影响因子: --
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Linkert M;Rueden CT;Allan C;Burel JM;Moore W;Patterson A;Loranger B;Moore J;Neves C;Macdonald D;Tarkowska A;Sticco C;Hill E;Rossner M;Eliceiri KW;Swedlow JR
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