人間の一般転写因子IIHは,RNAポリメラーゼIIのC端領域をリン酸化する

H Lu¹, L Zawel, L Fisher

¹Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854-5635.

Nature

|August 20, 1992

まとめ

RNAポリメラーゼIIカルボキシ末端ドメインのリン酸化が転写を制御する. 転写因子IIEによって調節される一般的な転写因子IIH (TFIIH) キナーゼ活性はこの重要なステップに影響を与えます.

科学分野:

分子生物学は分子生物学である.
遺伝子発現の規制について
バイオケミストリーバイオケミストリー

背景:

転写開始から延長への移行は,遺伝子発現における重要な規制ポイントです.
RNAポリメラーゼIIのカルボキシ末端領域 (CTD) のリン酸化は,この移行における重要な出来事です.
TFIIHとTFIIEを含む一般的な転写因子は,転写の開始と延長を調節する上で重要な役割を果たします.

研究の目的:

CTDのリン酸化におけるTFIIH関連キナーゼ活動の役割を調査する.
TFIIHキナーゼの活性とプロセス性に対する転写因子IIEの影響を明らかにする.
これらの要因がどのように協調して,転写開始と延伸の間のスイッチを調節するかを理解する.

主な方法:

精製された転写因子とRNAポリメラーゼIIを用いたインビトロキナーゼアッセイ.
転写因子IIEの存在または欠如におけるTFIIHキナーゼ活性に関する分析.
TFIIH-TFIIE複合体の形成の生化学的特徴と,キナーゼプロセシビティへの影響.

主要な成果:

TFIIHは,RNAポリメラーゼII CTD.をリン酸化できる固有キナーゼ活性を有しています.
RNAポリメラーゼIIとプレイニシテーション複合体の結合を促進する因子は,TFIIHキナーゼの活性を増強する.
転写因子IIEは,前始動複合体内でTFIIHを安定させ,そのキナーゼプロセシビティを調節する.

結論:

TFIIH媒介CTDリン酸化は,転写開始-延長移行を制御する重要なメカニズムです.
TFIIEは,TFIIHキナーゼの活性性の安定性と過程性に影響することで,規制的な役割を果たします.
これらの発見は,遺伝子発現を調節する一般的な転写因子の協調作用に関する洞察を提供します.

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