Fanzors, a family of eukaryotic RNA-guided DNA endonucleases.

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Kaiyi Jiang, Jonathan S Gootenberg, Omar O Abudayyeh
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引用次数: 0

Abstract

Fanzor proteins represent the first confirmed family of RNA-guided DNA endonucleases in eukaryotes. Originally identified in 2013 as TnpB homologs, Fanzors remained functionally uncharacterized until 2023, when three independent research groups demonstrated their activity as programmable nucleases. Comprehensive bioinformatic analysis revealed over 3000 unique Fanzor sequences across diverse eukaryotic phyla and viruses. Fanzors share core mechanisms with their prokaryotic counterparts, utilizing a RuvC domain for DNA cleavage and requiring a Fanzor RNA (ωRNA) for targeting. However, they exhibit distinctive features, including diverse target adjacent motif preferences, extended ωRNA structure, and RuvC domain rearrangements. The eukaryotic origins of Fanzors make them promising tools for mammalian genome editing, with initial studies demonstrating successful editing in human cells without extensive engineering.

真核生物rna引导的DNA内切酶家族。
Fanzor蛋白代表了真核生物中第一个被证实的rna引导DNA内切酶家族。Fanzors最初在2013年被鉴定为TnpB同源物,直到2023年,三个独立的研究小组证明了它们作为可编程核酸酶的活性,才对其功能进行了鉴定。综合生物信息学分析揭示了3000多个独特的Fanzor序列,跨越不同的真核生物门和病毒。Fanzor与它们的原核生物具有相同的核心机制,利用RuvC结构域进行DNA切割,并需要一个Fanzor RNA (- RNA)来靶向。然而,它们表现出不同的特征,包括不同的目标邻近基序偏好,扩展的ωRNA结构和RuvC结构域重排。Fanzors的真核起源使其成为哺乳动物基因组编辑的有希望的工具,初步研究表明,无需大量工程就可以在人类细胞中成功编辑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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