生物
清脆的
DNA
核糖核酸
核酸酶
免疫
核心
病毒学
遗传学
细胞生物学
基因
免疫系统
作者
David Mayo-Muñoz,Lisa F. Smith,Carmela Garcia-Doval,Lucia M Malone,Kate R. Harding,Simon A. Jackson,Hannah G Hampton,Robert D. Fagerlund,Laura F. Gumy,Peter C. Fineran
出处
期刊:Molecular Cell
[Elsevier]
日期:2022-12-01
卷期号:82 (23): 4471-4486.e9
被引量:11
标识
DOI:10.1016/j.molcel.2022.10.028
摘要
Bacteria have diverse defenses against phages. In response, jumbo phages evade multiple DNA-targeting defenses by protecting their DNA inside a nucleus-like structure. We previously demonstrated that RNA-targeting type III CRISPR-Cas systems provide jumbo phage immunity by recognizing viral mRNA exported from the nucleus for translation. Here, we demonstrate that recognition of phage mRNA by the type III system activates a cyclic triadenylate-dependent accessory nuclease, NucC. Although unable to access phage DNA in the nucleus, NucC degrades the bacterial chromosome, triggers cell death, and disrupts phage replication and maturation. Hence, type-III-mediated jumbo phage immunity occurs via abortive infection, with suppression of the viral epidemic protecting the population. We further show that type III systems targeting jumbo phages have diverse accessory nucleases, including RNases that provide immunity. Our study demonstrates how type III CRISPR-Cas systems overcome the inaccessibility of jumbo phage DNA to provide robust immunity.
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