CRISPR関連エンドペプチダゼによるRNA活性化タンパク質分裂

Jonathan Strecker^1,2,3,4,5, F Esra Demircioglu^1,2,3,4,5, David Li^1,2,3,4,5,6

¹Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Science (New York, N.Y.)

|November 24, 2022

まとめ

研究者はCRISPR関連プロテアゼ (CASP) を発見し,遺伝子の活動を制御するためにRNAを使用しています. このRNA誘導酵素は,様々な用途でRNA感知技術の開発に新しい可能性を秘めています.

科学分野:

微生物学
分子生物学
生物化学

背景:

プロカリオットのCRISPR-Casシステムは,RNA誘導核酸によって適応免疫を提供する.
非核酶機能を持つ関連遺伝子は,RNA誘導酵素のより広範な役割を示唆する.
*Desulfonema ishimotonii* のCsx29遺伝子は,CRISPRエフェクターCas7-11に関連したプロテアスをコードする.

研究の目的:

CRISPR関連プロテアゼ (CASP) Csx29の機能を調査する.
RNA 誘導酵素活動のメカニズムを解明する.
このRNA感知能力の潜在的応用を探求する.

主な方法:

プロテアゼの活性を示すための生化学的測定
電子顕微鏡で複雑な構造を特定する
実験室内およびヒト細胞ベースの実験で

主要な成果:

Csx29 (CASP) はプログラム可能なRNA活性化エンドペプチダース活性を示しています.
プロテアゼはシグマ因子阻害剤を標的とし,転写反応を調節する.
Cryo-EMは標的RNA結合に依存するアロステル活性化メカニズムを示した.

結論:

プログラム可能な活性を持つ新しいRNA誘導タンパク質を発見した.
RNA活性化酵素機能のアロステルメカニズムを明らかにした.
このRNA誘導機能は,RNAセンシングアプリケーションを開発する可能性を秘めています.

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