小柯机器人

美国麻省理工学院张锋研究小组发现，Fanzor是一种真核生物可编程的RNA引导型内切酶。这一研究成果于2023年6月28日在线发表在国际学术期刊《自然》上。

研究人员表示，RNA引导系统利用引导RNA和靶标核酸序列之间的互补性来识别遗传元件，在原核生物和真核生物的生物过程中都发挥着核心作用。例如，原核生物CRISPR-Cas系统为细菌和古细菌提供了对外来遗传元素的适应性免疫。Cas效应器，如Cas9和Cas12，进行引导RNA依赖性DNA切割。尽管到目前为止已经研究了一些真核生物的RNA引导系统，如RNA干扰和核糖体RNA修饰，但仍不清楚真核生物是否有RNA引导的内切酶。最近，一个新的原核生物RNA引导系统（称为OMEGA）被报道。OMEGA效应物TnpB是Cas12的推定祖先，具有RNA引导的内切酶活性。TnpB也可能是真核生物转座子编码的Fanzor（Fz）蛋白的祖先，这提出了真核生物也配备了CRISPR-Cas/OMEGA类似的可编程RNA引导型内切酶的可能性。

研究人员报告了Fz的生化特性，表明它是一种RNA引导的DNA内切酶。研究人员还表明，Fz可以被重新编程用于人类基因组工程的应用。最后，研究人员用冷冻电镜在2.7埃分辨率下解析了Spizellomyces punctatus Fz（SpuFz）的结构，并揭示了Fz、TnpB和Cas12之间核心区域的保守性，尽管同源的RNA结构不同。这些研究结果表明，Fz是一个真核生物的OMEGA系统，并表明RNA引导型内切酶存在于生命的三个域中。

附：英文原文

Title: Fanzor is a eukaryotic programmable RNA-guided endonuclease

Author: Saito, Makoto, Xu, Peiyu, Faure, Guilhem, Maguire, Samantha, Kannan, Soumya, Altae-Tran, Han, Vo, Sam, Desimone, AnAn, Macrae, Rhiannon K., Zhang, Feng

Issue&Volume: 2023-06-28

Abstract: RNA-guided systems, which employ complementarity between a guide RNA and target nucleic acid sequences for recognition of genetic elements, play a central role in biological processes in both prokaryotes and eukaryotes. For example, the prokaryotic CRISPR-Cas systems provide adaptive immunity for bacteria and archaea against foreign genetic elements. Cas effectors, like Cas9 and Cas12, perform guide RNA-dependent DNA cleavage1. Although a few eukaryotic RNA-guided systems have been studied so far, such as RNA interference2 and ribosomal RNA modification3, it remains unclear whether eukaryotes have RNA-guided endonucleases. Recently, a new class of prokaryotic RNA-guided system (termed OMEGA) was reported4,5. The OMEGA effector TnpB is the putative ancestor of Cas12 and has RNA-guided endonuclease activity4,6. TnpB may also be the ancestor of the eukaryotic transposon-encoded Fanzor (Fz) proteins4,7, raising the possibility that eukaryotes are also equipped with CRISPR-Cas/OMEGA-like programmable RNA-guided endonucleases. Here we report the biochemical characterization of Fz, showing that it is an RNA-guided DNA endonuclease. We also show that Fz can be reprogrammed for human genome engineering applications. Finally, we resolved the structure of Spizellomyces punctatus Fz (SpuFz) at 2.7 using cryogenic-electron microscopy, revealing the conservation of the core regions among Fz, TnpB and Cas12, despite diverse cognate RNA structures. Our results show that Fz is a eukaryotic OMEGA system, demonstrating that RNA-guided endonucleases are present in all three domains of life.

DOI: 10.1038/s41586-023-06356-2

Source: https://www.nature.com/articles/s41586-023-06356-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html