ファグでコードされた抗CRISPRは,タイプVI-AのCRISPR-Cas免疫を完全に回避します

Alexander J Meeske¹, Ning Jia², Alice K Cassel¹

¹Laboratory of Bacteriology, The Rockefeller University, New York, NY 10065, USA.

Science (New York, N.Y.)

|May 30, 2020

まとめ

ウイルスはCRISPR-Casの免疫を回避できますリステリアファージの新種の抗CRISPRタンパク質 (AcrVIA1) は,Cas13a酵素を無効化し,RNAによる細菌の防御を完全に阻害する.

科学分野:

微生物学
分子生物学
生物化学

背景:

CRISPR-Casシステムは,バクテリアと古生物における外来核酸に対する適応免疫を提供します.
タイプVIのCRISPR-Casシステム,特にCas13はRNA分子を標的とし,RNAウイルスとプラズミドに対する防御を提供します.
ウイルスがVI型CRISPR-Cas免疫に抵抗するメカニズムは,まだほとんど研究されていない.

研究の目的:

タイプVI-AのCRISPR-Casシステムに敵対するウイルス要因を特定し,特徴づけること.
特定の抗CRISPRタンパク質がCas13aの活性を抑制するメカニズムを解明する.

主な方法:

リステリアファージ φLS46 と *Listeria seeligeri* のCRISPR-Casシステムの遺伝子解析
AcrVIA1の存在下でCas13a核酵素の活性を評価するための生化学的測定
AcrVIA1とCas13aの相互作用界面を決定するための構造生物学技術 (例えば,X線結晶学).

主要な成果:

リステリアファージ φLS46によってコードされた抗CRISPRタンパク質であるAcrVIA1の発見は,特に*Listeria seeligeri*型VI-A CRISPR-Casシステムを阻害する.
AcrVIA1はCas13aのガイドRNA結合面に結合し,標的RNAの認識と核酵素の活性化をステリカルに阻害する.
AcrVIA1を放出する1つのビリオンは,DNAを標的とするCas核酸の阻害剤とは異なり,タイプVI-AのCRISPR媒介免疫を完全に廃止するのに十分である.

結論:

ウイルスは,バクテリアのRNA標的免疫を克服するために,洗練された抗CRISPRメカニズムを進化させた.
AcrVIA1はCas13aの強力な阻害剤であり,CRISPR-Casシステムを操作するための新しいツールを提供します.
これらのウイルス対策を理解することは,CRISPR-Cas技術を含む効果的なファージ療法と合成生物学アプリケーションの開発に不可欠です.

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