2023-06-28 マサチューセッツ工科大学(MIT)
Pictured is a Cryo-EM map of a Fanzor protein (gray, yellow, light blue, and pink) in complex with ωRNA (purple) and its target DNA (red). A non-target DNA strand is in blue.
Image courtesy of the Zhang lab.
◆Fanzorシステムは、CRISPR-Casシステムよりも細胞や組織への送達が容易であり、ターゲティング効率を改善するためのさらなる改良により、人間のゲノム編集において有益な新技術となる可能性があります。
◆この研究は、RNAガイドのDNA切断メカニズムが生命のすべての界に存在することを示しています。この新しいシステムは、既存のゲノム編集ツールと補完し、人間の細胞で正確な変化をもたらす別の手段です。
<関連情報>
- https://news.mit.edu/2023/fanzor-system-in-animals-can-edit-human-genome-0628
- https://www.nature.com/articles/s41586-023-06356-2
Fanzorは真核生物のプログラム可能なRNAガイドエンドヌクレアーゼである。 Fanzor is a eukaryotic programmable RNA-guided endonuclease
Makoto Saito,Peiyu Xu,Guilhem Faure,Samantha Maguire,Soumya Kannan,Han Altae-Tran,Sam Vo,AnAn Desimone,Rhiannon K. Macrae & Feng Zhang
Nature Published:28 June 2023
DOI:https://doi.org/10.1038/s41586-023-06356-2
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.
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 2.7Å 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.
