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首页> 外文期刊>Nature >Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic oligoadenylate
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Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic oligoadenylate

机译：环核酸酶通过降解环状寡聚腺苷酸使III型CRISPR核糖核酸失活

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摘要

The CRISPR system provides adaptive immunity against mobile genetic elements in prokaryotes, using small CRISPR RNAs that direct effector complexes to degrade invading nucleic acids~(1-3). Type III effector complexes were recently demonstrated to synthesize a novel second messenger, cyclic oligoadenylate, on binding target RNA~(4,5). 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.
机译：CRISPR系统使用小型CRISPR RNA引导效应子复合物降解入侵的核酸（1-3），从而提供针对原核生物中移动遗传元件的适应性免疫力。最近证实III型效应物复合物在结合靶RNA〜（4,5）上合成了新型的第二信使，环状寡腺苷酸。环状低聚腺苷酸又通过CRISPR相关的Rossman折叠结构域与核糖核酸酶和其他因子结合并激活，从而在细胞中诱导对免疫至关重要的抗病毒状态。不了解重置系统的“关闭开关”的机制。在这里，我们确定了降解这些环状低聚腺苷酸环分子的核酸酶。这种“环核酸酶”本身就是CRISPR相关的Rossman-fold家族的一种蛋白质，并具有金属独立的机制，该机制可切割环状四腺苷酸环以生成线性二腺苷酸物种并关闭抗病毒状态。环核酸酶的鉴定为CRISPR系统增加了重要的见识。

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  • 来源
    《Nature》 |2018年第7726期|277-280|共4页
  • 作者

    Januka S Athukoralage; Christophe Rouillon; Shirley Graham; Sabine Grüschow; Malcolm F White;

  • 作者单位

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK;

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK;

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK;

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK;

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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