RNAポリメラーゼIIIの転写開始の構造的基礎
Guillermo Abascal-Palacios1, Ewan Phillip Ramsay1, Fabienne Beuron1
1The Institute of Cancer Research, London SW7 3RP, UK.
Nature
|January 19, 2018
まとめ
研究者は電子顕微鏡を用いてRNAポリメラーゼ (Pol) III転写開始複合体を視覚化しました. TFIIIBは,ポリマーゼの間の保存されたメカニズムを明らかにし,DNAの開きと転写の開始を促進するPol IIIの結合構造を再構築します.
科学分野:
- 分子生物学
- 構造生物学
- 生物化学
背景:
- RNAポリメラーゼ (Pol) IIIは,必須の非コーディングRNA (tRNA,5SrRNA,U6snRNA) を転写する.
- ポールIIIの放出は がんでは一般的です
- Pol IIIによる転写開始には,転写因子TFIIIBが前始動複合体 (PIC) を形成することが必要である.
研究 の 目的:
- Pol IIIの転写開始の構造的基礎を決定する.
- Pol III 初期化複合体 (PIC) と無結合の Pol III を視覚化する.
- ポールIII PIC形成とDNA開封におけるTFIIIBの役割を明らかにする.
主な方法:
- 低温電子顕微鏡 (cryo-EM) による再構築
- Pol IIIとPol III-TFIIIB-DNA複合体の高解像度構造分析
主要な成果:
- Pol III PICの3. 4-4. 0 Åの解像度構造と,無結合のapo-Pol IIIの3.1 Åの構造が得られた.
- TFIIIBはDNAを囲み,C37とC34のサブユニットを再配置するサブユニットBdp1でPol IIIを再構成する.
- DNAの開きが促進され,解き放たれたDNAはPol III裂け目に接触する.
- Pol III PICの構造は,Pol II PICにトポロジ的に似ていますが,Pol I PICとは異なります.
結論:
- 構造は,Pol IIIの転写開始の分子メカニズムを明らかにします.
- TFIIIB結合はDNA開きとPIC形成に不可欠である.
- 異なったRNAポリメラーゼにわたって保存された転写開始機構が存在する.
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