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一个自然的单导向RNA重新定位Cas9以自我调节CRISPR-Cas的表达

Rachael E Workman¹, Teja Pammi¹, Binh T K Nguyen¹

¹Department of Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

|January 9, 2021

概括

克里斯普尔-卡斯系统由自然单一导向RNA调节,该导向RNA抑制其自身的促进子,从而平衡病毒免疫与自身免疫毒性. 这种自我调节在II-A型系统中很普遍,有助于水平基因转移.

科学领域:

微生物学
分子生物学
遗传学

背景情况:

克里斯普尔-卡斯系统赋予 prokaryotes 对外基因元素的适应性免疫力.
调节CRISPR-Cas系统以防止自我向 (自身免疫) 的机制在很大程度上是未知的.

研究的目的:

在Streptococcus pyogenes中研究CRISPR-Cas系统的调节机制.
阐明转激活CRISPRRNA (tracrRNA) 在CRISPR-Cas系统调节中的作用.

主要方法:

长形式的交互激活CRISPRRNA (tracr-L) 的结构分析.
功能性测试以评估tracr-L对Cas9活动和促进体抑制的影响.
在II-A型CRISPR-Cas系统中对tracrRNA介导自调的生物信息分析.

主要成果:

tracr- L 作为一种天然的单一导向RNA,指导 Cas9 抑制其自身的促进子 (P_cas).
抑制P_cas导致抗病毒免疫增加3000倍,但也增加了自身免疫毒性.
有证据表明,在II-A型CRISPR-Cas系统中,tracrRNA介导的自我调节是常见的.

结论:

通过自然单向导RNA揭示了CRISPR-Cas系统内在调节的新范式.
这种自我调节机制平衡了增强免疫的好处和自身免疫的风险.
这些发现可能解释了CRISPR-Cas系统频繁地向新宿主转移.

关键词:

在CRISPR-Cas 其他国家自体免疫性细菌的调节细菌菌体在这是一个很好的例子.这样就好了.

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