TCAB1によって形成され,RNA構成に基づくヒトテロメラーゼの活性スイッチ

Lu Chen¹, Caitlin M Roake¹, Adam Freund¹

¹Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

Cell

|May 29, 2018

まとめ

テロメラーゼの活動は,ヒトテロメラーゼRNA (hTR) の構成を制御するタンパク質TCAB1に依存しています. これはテロメラーゼ触媒とTERT結合を調節するスイッチを明らかにし,がんと幹細胞生物学に影響を与えています.

科学分野:

分子生物学
生物化学
遺伝学

背景:

リボ核タンパク質酵素は,触媒化のためにダイナミックなRNA構造を必要とします.
人間のテロメラーゼ (hTR) は,未知のメカニズムで触媒を刺激するコアとCR4/5の接点を持っています.

研究の目的:

ヒトのテロメラーゼ活性における TCAB1 の役割を明らかにする.
TCAB1がhTRのCR4/5ドメインの構成にどのように影響するか理解する.
CR4/5コンフォーム,TERT結合,テロメラーゼ触媒との関連を調査する.

主な方法:

TCAB1 を欠く細胞におけるテロメラーゼ活性の研究
TCAB1の無活性化によるCR4/5ヘリクスの構造変化を分析した.
テロメラーゼ機能に対する患者由来CR4/5変異の影響を調べました.

主要な成果:

TCAB1はテロメラーゼの触媒作用に不可欠であり,酵素組成とは関係ありません.
TCAB1の枯渇はCR4/5ヘリクスの展開を引き起こし,TERT関連性を損なう.
CR4 / 5変異は,触媒とTERT結合に対するTCAB1不活性化効果を模倣する.

結論:

TCAB1は,hTR CR4/5の構成を制御することによって,テロメラーゼの重要な調節剤として作用する.
hTRのコンフォメーションスイッチはテロメラーゼ触媒とTERTの関与を制御する.
テロメラーゼの2つの異なる触媒状態は,がんおよび前身細胞に関連する分子内調節を示唆する.

キーワード:

CABボックス CR4/5 についてカジャルの体 H/ACA RNP について RNAの折りたたみ TCAB1 について生まれながらの発酵不全 icSHAPE についてテロメラーゼテロメア

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