RNAは,プリオンのようなRNA結合タンパク質の相分離行動をバッファリングする
Shovamayee Maharana1, Jie Wang1, Dimitrios K Papadopoulos1,2
1Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany.
まとめ
RNA濃度は,プリオンのようなRNA結合タンパク質 (RBPs) の振る舞いを決定する. 高濃度の核RNAはRBPの溶解性を維持し,低濃度または劣化したRNA結合は有害な結合を誘発する.
科学分野:
- 分子生物学
- 細胞生物学
- 生物化学
背景:
- TDP43およびFUSを含むプリオン型のRNA結合タンパク質 (RBPs) は,通常,核に溶けます.
- これらのタンパク質は サイトプラズマで 病理的集積を形成します
- 核溶解性と細胞プラズマ結合を制御するメカニズムは不明である.
研究 の 目的:
- プリオンのようなRBPの相行動の調節におけるRNAの役割を調査する.
- RNA濃度がRBPの溶解性と結合にどのように影響するかを理解する.
- RBPの誤局と集積に寄与する要因を解明する.
主な方法:
- 異なったRNA/タンパク質比率で in vitro 段階分離試験を行う.
- 核RNAのレベルを減らすための細胞実験
- RBPsのRNA結合能力を破壊する 遺伝子操作です
主要な成果:
- In vitroでは,低いRNA/タンパク質比が液滴形成を促進し,高い比がそれを阻害した.
- 細胞内の核RNAの結合が低下したり,過度の相分離を引き起こした.
- これらの細胞の変化は,細胞毒性固体のような RBP アセンブリの形成につながった.
結論:
- RNA濃度は,プリオンのようなRBP相行動の重要なレギュラーである.
- 核は,RBPの溶解性を維持する高いRNA濃度を持つバッファリングシステムとして機能する.
- RBPの異常な相移行は,RNAレベルまたはRNA結合の変化と関連しています.
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