Cas9 切割病毒基因组可诱导新免疫记忆的获得。
Cas9 Cleavage of Viral Genomes Primes the Acquisition of New Immunological Memories.
机构信息
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; Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA.
出版信息
Cell Host Microbe. 2019 Oct 9;26(4):515-526.e6. doi: 10.1016/j.chom.2019.09.002. Epub 2019 Oct 1.
Type II CRISPR-Cas systems defend prokaryotes from bacteriophage infection through the acquisition of short viral DNA sequences known as spacers, which are transcribed into short RNA guides to specify the targets of the Cas9 nuclease. To counter the potentially devastating propagation of escaper phages with mutations in the target sequences, the host population acquires many different spacers. Whether and how pre-existing spacers in type II systems affect the acquisition of new ones is unknown. Here, we demonstrate that previously acquired spacers promote additional spacer acquisition from the vicinity of the target DNA site cleaved by Cas9. Therefore, CRISPR immune cells acquire additional spacers at the same time as they destroy the infecting virus. This anticipates the rise of escapers or related viruses that could escape targeting by the first spacer acquired. Our results thus reveal Cas9's role in the generation of immunological memories.
II 型 CRISPR-Cas 系统通过获取短的病毒 DNA 序列（称为间隔序列）来防御原核生物免受噬菌体的感染，这些间隔序列被转录成短的 RNA 向导，以指定 Cas9 核酸酶的靶标。为了抵御靶序列突变的逃逸噬菌体的潜在破坏性传播，宿主群体获得了许多不同的间隔序列。II 型系统中以前存在的间隔序列是否以及如何影响新间隔序列的获取尚不清楚。在这里，我们证明了以前获得的间隔序列促进了 Cas9 切割靶 DNA 位点附近的新间隔序列的获取。因此，CRISPR 免疫细胞在破坏感染病毒的同时获得额外的间隔序列。这可以预测第一批获得的间隔序列可能无法靶向的逃逸者或相关病毒的出现。因此，我们的研究结果揭示了 Cas9 在免疫记忆产生中的作用。
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