Abstract：
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.
摘要：
细菌对噬菌体有多种防御。作为回应,巨型噬菌体通过保护它们的DNA在类似细胞核的结构内逃避了多种DNA靶向防御。我们先前证明，靶向RNA的III型CRISPR-Cas系统通过识别从细胞核输出的病毒mRNA进行翻译来提供巨大的噬菌体免疫。这里,我们证明了III型系统对噬菌体mRNA的识别会激活环状三腺苷酸依赖性辅助核酸酶，NucC.尽管无法获取细胞核中的噬菌体DNA，NucC降解细菌染色体,引发细胞死亡,破坏噬菌体复制和成熟.因此，III型介导的巨型噬菌体免疫通过流产感染发生，抑制病毒流行保护人口。我们进一步表明，针对巨型噬菌体的III型系统具有不同的辅助核酸酶，包括提供免疫力的核糖核酸酶。我们的研究证明了III型CRISPR-Cas系统如何克服巨型噬菌体DNA的不可接近性，以提供强大的免疫力。
