ファンゾールは,真核生物のプログラム可能なRNA誘導エンドヌクレアゼである
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
まとめ
ユカリオットは,Fanzor (Fz) タンパク質によって示されるRNA誘導のエンドヌクレアスを有しており,これはゲノム工学にとって極めて重要です. この発見は 生命の3つの領域にわたる RNA誘導システムを 確認しています
科学分野:
- 分子生物学
- 遺伝学
- 生物化学
背景:
- CRISPR-CasのようなRNA誘導システムは 適応免疫とDNA分裂に不可欠です
- ユカリオットのRNA誘導系はあまり理解されていないが,RNA誘導性エンドヌクレアスは確認されていない.
- TnpBを含むプロカリオットOMEGAシステムは,真核Fanzor (Fz) タンパク質との祖先を共有しています.
研究 の 目的:
- Fanzor (Fz) タンパク質の生化学的特徴を明らかにする.
- ヒトゲノム工学における Fzの再プログラムの可能性を調査する
- FzのRNA誘導DNAエンドヌクレアース活動の構造的基礎を解明する.
主な方法:
- Fzの核酵素活性を決定する生化学分析
- Fzをプログラムして ヒトの細胞にDNAを 分割する
- Fzの構造分析のための冷凍電子顕微鏡 (cryo-EM)
主要な成果:
- Fanzor (Fz) タンパク質はRNA誘導DNAエンドヌクレアースとして機能する.
- Fzは,ゲノム編集アプリケーションのために成功裏に設計することができます.
- 構造分析では,Fz,TnpB,Cas12の間の保存された領域が示されています.
結論:
- ファンゾール (Fz) はエウカリオットOmegaシステムを表しています.
- RNA誘導型エンドヌクレアゼは,生命の3つの領域 (細菌,古生物,真核生物) に存在している.
- Fzはユカリオットゲノム工学のツールキットを拡張します.
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