Diverse virus-encoded CRISPR-Cas systems include streamlined genome editors
Diverse virus-encoded CRISPR-Cas systems include streamlined genome editors
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DOI：
10.1016/j.cell.2022.10.020
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发表时间：
2022-11-23
期刊：
影响因子：
64.5
通讯作者：
Doudna, Jennifer A.
中科院分区：
文献类型：
--
作者：
Al-Shayeb, Basem;Skopintsev, Petr;Doudna, Jennifer A.
CRISPR-Cas系统是宿主编码的途径，使用自适应RNA引导机制保护微生物免受病毒感染。使用基因组解析宏基因组学，我们发现CRISPR系统也在不同的噬菌体中编码，它们作为发散和超紧凑的抗病毒系统出现。噬菌体编码的CRISPR系统属于所有六种已知的CRISPR-Cas类型，尽管有些缺乏关键成分，这表明替代功能作用或宿主互补。我们描述了多种新的Cas9样蛋白和44个与V型CRISPR-Cas系统相关的家族，包括Cas lambda RNA指导的核酸酶家族。在已鉴定的最具差异性的新酶中，Cas lambda使用独特结构的CRISPR RNA（crRNA）识别双链DNA。通过冷冻电子显微镜确定的Cas plasmoda-RNA-DNA结构揭示了能够在哺乳动物、拟南芥和六倍体小麦细胞中诱导基因组编辑的紧凑的双叶结构。这些发现揭示了CRISPR-Cas酶的新来源，并强调了它们作为植物和人类细胞基因组编辑器的价值。
CRISPR-Cas systems are host-encoded pathways that protect microbes from viral infection using an adaptive RNA-guided mechanism. Using genome-resolved metagenomics, we find that CRISPR systems are also encoded in diverse bacteriophages, where they occur as divergent and hypercompact anti-viral systems. Bacteriophage-encoded CRISPR systems belong to all six known CRISPR-Cas types, though some lack crucial components, suggesting alternate functional roles or host complementation. We describe multiple new Cas9-like proteins and 44 families related to type V CRISPR-Cas systems, including the Cas lambda RNA-guided nuclease family. Among the most divergent of the new enzymes identified, Cas lambda recognizes double-stranded DNA using a uniquely structured CRISPR RNA (crRNA). The Cas lambda-RNA-DNA structure determined by cryoelectron microscopy reveals a compact bilobed architecture capable of inducing genome editing in mammalian, Arabidopsis, and hexaploid wheat cells. These findings reveal a new source of CRISPR-Cas enzymes in phages and highlight their value as genome editors in plant and human cells.