Aviram Naama, Shilton Amanda K, Lyn Nia G, Reis Bernardo S, Brivanlou Amir, Marraffini Luciano A
Laboratory of Bacteriology, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA.
Laboratory of Bacteriology, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA.
Cell Host Microbe. 2024 Dec 11;32(12):2050-2062.e6. doi: 10.1016/j.chom.2024.11.005. Epub 2024 Dec 2.
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.
来自所有生命王国的细胞在不利的环境条件下都会进入生长停滞状态。这一过程的关键是能够从这种状态恢复的机制。葡萄球菌III-A型CRISPR-Cas基因座编码Cas10复合体，该复合体利用引导RNA定位互补的病毒转录本并启动免疫反应。当靶序列在病毒裂解周期后期表达时，防御需要Csm6的活性，Csm6是一种非特异性核糖核酸酶，可抑制受感染细胞的生长。Csm6如何保护细胞免受感染以及生长是否能够恢复尚不清楚。在这里，我们表明生长停滞在群体水平上提供了免疫，防止病毒复制并使未感染的细胞得以增殖。此外，Cas10的单链脱氧核糖核酸酶活性是一部分停滞细胞重新生长和受感染宿主恢复所必需的，大概是通过降解病毒DNA来结束免疫反应。
