タイプIIIのCRISPR-Casシステムにおける周期性オリゴヌクレオチドシグナル伝達経路

Migle Kazlauskiene¹, Georgij Kostiuk¹, Česlovas Venclovas¹

¹Institute of Biotechnology, Vilnius University, Saulėtekio Avenue 7, 10257 Vilnius, Lithuania.

Science (New York, N.Y.)

|July 1, 2017

まとめ

タイプIIIのCRISPR-Casシステムは,Csm複合体を用いてDNAとRNAを分解する. 周期性オリゴアデニラートはCsm6にRNAを分解し,ファグに対する防御を調整する信号を与える.

科学分野:

分子生物学
微生物学
免疫学

背景:

タイプIIIのCRISPR-Casシステムは,外来核酸に対するプロカリオット免疫を提供します.
Csmエフェクター複合体は,Cas10とCsm6を含むDNAとトランスクリプトを分解する.
Cas10のPalmドメインの機能とCsm6の役割は完全に理解されていません.

研究の目的:

タイプIIIのCRISPR-CasシステムにおけるCas10のPalmドメインの機能を明らかにする.
CRISPR-Cas免疫における周期性オリゴアデニラートの役割を理解する.
Csm複合体とCsm6の活動を調整するシグナルメカニズムを詳細に説明します.

主な方法:

ストレプトコッカス・サーモフィラスのCsmエフェクター複合体を研究した.
Cas10による循環性オリゴアデニラートの合成を分析した.
循環性オリゴアデニラートとCsm6の相互作用とRNAの分解への影響を研究した.

主要な成果:

標的RNA結合は,Cas10のPalmドメインを活性化し,周期性オリゴアデニラート (cA2- 6) を合成する.
循環性オリゴアデニラートは,シグナル伝達分子として作用し,Csm6を結合および活性化します.
活性化されたCsm6は非特異的なRNAを分解し,ファグの防御に寄与する.

結論:

周期性オリゴアデニラート媒介の信号経路がCRISPR-Casの構成要素を調整する.
この経路は,ファグの感染に対するプロカリオット免疫を強化します.
この研究は,CRISPR-Casの抗ウイルス防御を調節する新しいメカニズムを明らかにしています.

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