Fanzor是一种可编程RNA导向的真核内核酶
Makoto Saito1,2,3,4,5, Peiyu Xu1,2,3,4,5, Guilhem Faure1,2,3,4,5
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nature
|June 28, 2023
概括
细胞具有RNA引导的内核酶,以Fanzor (Fz) 蛋白质为例,这些蛋白质对基因组工程至关重要. 这一发现证实了RNA指导系统在生命的三个领域.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 像CRISPR-Cas这样的RNA导向系统对于原生生物的适应性免疫和DNA分裂至关重要.
- 细胞RNA引导系统的理解较少,没有确认RNA引导的内核酶.
- Prokaryotic OMEGA 系统,包括 TnpB,与真核Fanzor (Fz) 蛋白质有共同的祖先.
研究的目的:
- 在生物化学上描述Fanzor (Fz) 蛋白质.
- 调查Fz在人类基因组工程中的重编程潜力.
- 阐明Fz的RNA导向DNA内核酶活动的结构基础.
主要方法:
- 生物化学测试以确定Fz的核酶活性.
- 在人类细胞中重新编程Fz以进行向DNA裂变.
- 低温电子显微镜 (cryo-EM) 用于Fz的结构分析.
主要成果:
- 范泽 (Fz) 蛋白质作为RNA指导的DNA内核酶起作用.
- 可以成功地为基因组编辑应用设计Fz.
- 结构分析显示Fz,TnpB和Cas12之间的保护区域.
结论:
- 范佐尔 (Fz) 是一个真核生物的OMEGA系统.
- 在生命的三个领域 (细菌,古生物和真核生物) 都存在RNA引导的内核酶.
- Fz扩展了真核基因组工程的工具包.
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