7SK小核RNAは,CDK9/サイクリンT複合体の活性に結合し,それを阻害する
V T Nguyen1, T Kiss, A A Michels
1Génétique Moléculaire, UMR 8541 CNRS, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris cedex 05, France.
Nature
|November 20, 2001
まとめ
P-TEFbと7SKRNAを含む新たに発見された複合体は,RNAポリメラーゼIIの活性を調節する. この複合体はP-TEFbを隔離し,転写が阻害されるまでキナーゼ活性を低下させ,フィードバックメカニズムを示唆します.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- バイオケミストリー バイオケミストリー
背景:
- ユカリオット遺伝子の転写はRNAポリメラーゼII (Pol II) 活動によって制御される.
- P-TEFbによるPol II CTDのリン酸化は,転写の延長に不可欠である.
- P-TEFbはCDK9とサイクリンT1またはT2で構成されています.
研究 の 目的:
- P-TEFb活動の調節を調査する.
- P-TEFbと相互作用する新しい要因を特定する.
- 転写調節における7SKRNAの役割を理解する.
主な方法:
- 細胞分断とヒトHeLa細胞からの複雑な分離.
- バイオケミカルアッセイでキナーゼ活性を測定する.
- 様々な条件下でのP-TEFb/7SK複合体の形成と破壊の分析.
主要な成果:
- 細胞のP-TEFbの半分以上は,7SK RNA.を持つ大きな複合体で見つかりました.
- これらの大きな7SK/P-TEFb複合体は,自由P-TEFbと比較して,CDK9キナーゼの活性が著しく低下しています.
- 転写の阻害は7SK/P-TEFb複合体の破壊とCDK9活性の増加につながります.
結論:
- 7SKRNAはP-TEFbを隔離し,RNA Pol IIの活性を調節する不活性複合体を形成する.
- P-TEFb/7SKの相互作用は,転写に依存するフィードバックメカニズムを表しています.
- この発見は,真核生物の遺伝子転写のための新しい調節経路を明らかにしています.
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