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Cas10 relieves host growth arrest to facilitate spacer retention during type III-A CRISPR-Cas immunity
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-12-02 , DOI: 10.1016/j.chom.2024.11.005
Naama Aviram, Amanda K. Shilton, Nia G. Lyn, Bernardo S. Reis, Amir Brivanlou, Luciano A. Marraffini

Cells from all kingdoms of life can enter growth arrest in unfavorable environmental conditions. Key to this process are mechanisms enabling recovery from this state. Staphylococcal type III-A CRISPR-Cas loci encode the Cas10 complex that uses a guide RNA to locate complementary viral transcripts and start an immune response. When the target sequence is expressed late in the viral lytic cycle, defense requires the activity of Csm6, a non-specific RNase that inhibits the growth of the infected cell. How Csm6 protects from infection and whether growth can be restored is not known. Here, we show that growth arrest provides immunity at the population level, preventing viral replication and allowing uninfected cells to propagate. In addition, the ssDNase activity of Cas10 is required for the regrowth of a subset of the arrested cells and the recovery of the infected host, presumably ending the immune response through degradation of the viral DNA.

中文翻译:


Cas10 缓解宿主生长停滞,促进 III-A 型 CRISPR-CAS 免疫期间的间隔区保留



来自所有生命王国的细胞都可以在不利的环境条件下进入生长停滞状态。此过程的关键是能够从此状态恢复的机制。葡萄球菌 III-A 型 CRISPR-Cas 基因座编码 Cas10 复合物,该复合物使用向导 RNA 定位互补病毒转录物并启动免疫反应。当靶序列在病毒裂解周期的晚期表达时,防御需要 Csm6 的活性,Csm6 是一种抑制感染细胞生长的非特异性 RNase。Csm6 如何防止感染以及是否可以恢复生长尚不清楚。在这里,我们表明生长停滞在群体水平上提供免疫力,防止病毒复制并允许未感染的细胞繁殖。此外,Cas10 的 ssDNase 活性是被停滞细胞子集的再生和受感染宿主的恢复所必需的,可能通过降解病毒 DNA 来结束免疫反应。
更新日期:2024-12-02
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