The CRISPR system provides adaptive immunity against mobile genetic elements in prokaryotes, using small CRISPR RNAs that direct effector complexes to degrade invading nucleic acids1–3. Type III effector complexes were recently demonstrated to synthesize a novel second messenger, cyclic oligoadenylate, on binding target RNA4,5. Cyclic oligoadenylate, in turn, binds to and activates ribonucleases and other factors—via a CRISPR-associated Rossman-fold domain—and thereby induces in the cell an antiviral state that is important for immunity. The mechanism of the ‘off-switch’ that resets the system is not understood. Here we identify the nuclease that degrades these cyclic oligoadenylate ring molecules. This ‘ring nuclease’ is itself a protein of the CRISPR-associated Rossman-fold family, and has a metal-independent mechanism that cleaves cyclic tetraadenylate rings to generate linear diadenylate species and switches off the antiviral state. The identification of ring nucleases adds an important insight to the CRISPR system.In the CRISPR type III system, ‘ring’ nucleases possess a metal-independent mechanism that cleaves cyclic oligoadenylate ring molecules to switch off the antiviral state in cells.

中文翻译：

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环状核酸酶通过降解环状寡聚腺苷酸使 III 型 CRISPR 核糖核酸酶失活

CRISPR 系统使用小的 CRISPR RNA 引导效应复合物降解入侵的核酸，从而提供针对原核生物中移动遗传元件的适应性免疫1-3。最近证明 III 型效应复合物可在结合靶标 RNA4,5 上合成新型第二信使环状寡腺苷酸。反过来，环状寡聚腺苷酸结合并激活核糖核酸酶和其他因子——通过 CRISPR 相关的罗斯曼折叠结构域——从而在细胞中诱导一种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，我们确定了降解这些环状寡聚腺苷酸环分子的核酸酶。这种“环状核酸酶”本身就是 CRISPR 相关罗斯曼折叠家族的一种蛋白质，并且具有不依赖金属的机制，可裂解环状四腺苷酸环以生成线性二腺苷酸种类并关闭抗病毒状态。环状核酸酶的鉴定为 CRISPR 系统增添了重要的洞察力。在 CRISPR III 型系统中，“环状”核酸酶具有不依赖金属的机制，可裂解环状寡聚腺苷酸环分子以关闭细胞中的抗病毒状态。