美国加州大学伯克利分校Jennifer A. Doudna等研究人员合作发现，多样化的病毒编码CRISPR-Cas系统包含精简的基因组编辑器。这一研究成果发表在2022年11月23日出版的国际学术期刊《细胞》上。
利用基因组解析元组学，研究人员发现CRISPR系统在不同的噬菌体中也有编码，在那里它们作为不同的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，表明有交替的功能作用或宿主互补。研究人员描述了多个新的Cas9样蛋白和44个与V型CRISPR-Cas系统相关的家族，包括Casλ RNA引导的核酸酶家族。在所发现的新酶中，Casλ是最不同的，它使用一种独特结构的CRISPR RNA（crRNA）识别双链DNA。通过冷冻电子显微镜确定的Casλ-RNA-DNA结构显示了一个紧凑的双叶结构，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。
这些发现揭示了噬菌体中CRISPR-Cas酶的一个新来源，并强调了它们作为植物和人类细胞中基因组编辑的价值。
据介绍，CRISPR-Cas系统是宿主编码的途径，其利用适应性RNA引导机制保护微生物免受病毒感染。
附：英文原文
Title: Diverse virus-encoded CRISPR-Cas systems include streamlined genome editors
Author: Basem Al-Shayeb, Petr Skopintsev, Katarzyna M. Soczek, Elizabeth C. Stahl, Zheng Li, Evan Groover, Dylan Smock, Amy R. Eggers, Patrick Pausch, Brady F. Cress, Carolyn J. Huang, Brian Staskawicz, David F. Savage, Steven E. Jacobsen, Jillian F. Banfield, Jennifer A. Doudna
Issue&Volume: 2022/11/23
Abstract: 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 Casλ RNA-guided nuclease family. Among the most divergent of the new enzymes identified, Casλ recognizes double-stranded DNA using a uniquely structured CRISPR RNA (crRNA). The Casλ-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.
DOI: 10.1016/j.cell.2022.10.020
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01366-6