RNA化学プロテオミクスは,N6-メチラデノシン (m6A) 調節されたタンパク質-RNA相互作用を明らかにする
A Emilia Arguello1, Amanda N DeLiberto1, Ralph E Kleiner1
1Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
Journal of the American Chemical Society
|November 16, 2017
まとめ
この研究は,N6-メチラデノシン (m6A) のRNAの改変がタンパク質の相互作用にどのように影響するかを明らかにしています. 研究者はm6Aを結合する新しいタンパク質を特定し,それがストレス粒子のタンパク質結合を妨げることを発見しました.
科学分野:
- 生物化学
- 分子生物学
- プロテオミクス
背景:
- エピトランスクリプトミックRNAの改変はmRNAの機能を調節する.
- RNA 改変効果の生化学的メカニズムは十分に理解されていません.
- N6-メチラデノシン (m6A) は,真核生物で最も豊富に存在する内部RNA変異である.
研究 の 目的:
- m6Aによって調節されるRNA-タンパク質の相互作用をプロファイルするための化学プロテオミクスアプローチを開発する.
- m6A型RNAと相互作用するタンパク質を識別する.
- m6Aの機能の生化学的メカニズムを解明する.
主な方法:
- 化学プロテオミクス戦略の開発
- 合成ダイアジリン含有RNAプローブとの写真クロスリンクを使用します.
- 定量プロテオミクスは,RNAとタンパク質の相互作用をプロファイルします.
主要な成果:
- 既知のm6Aインタラクター (YTHドメインタンパク質,ALKBH5) を特定した.
- 新しい m6A 読者: FMR1 と LRPPRC が発見され,ヒトの病気に関連しているタンパク質です.
- m6Aは,ストレス粒子のタンパク質 (G3BP1/2,USP10,CAPRIN1,RBM42) によってRNA結合を妨害することを発見した.
結論:
- この研究は,RNA 改変のインタラクトームを尋問するための一般的な戦略を示している.
- m6A機能の基礎となる新しい生化学的メカニズムを明らかにした.
- ストレス粒子の動態と疾患に関連するタンパク質の相互作用を調節する m6A の役割を強調した.
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