E3リガースネットワークは,GCN1を巻き込み,停止したリボソームの翻訳因子の分解を促進する

Keely Oltion¹, Jordan D Carelli¹, Tangpo Yang²

¹Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.

Cell

|January 13, 2023

まとめ

研究者は,リボソームをモニタリングすることによって,延伸因子-1α (eEF1A) を含む,停止した翻訳因子を分解する新しい品質管理経路を発見しました.

科学分野:

分子生物学
細胞生物学
生物化学

背景:

mRNA翻訳中のリボソームの停滞は,プロテオスタシスを維持するための品質管理経路を活性化します.
閉塞したA部位を持つ停止したリボソームを特定するメカニズムは捉え難いままです

研究の目的:

遮断されたA部位を持つリボソームに反応する監視メカニズムを特定する.
変換因子の劣化に関与するシグナルネットワークを解明する.

主な方法:

延長因子-1α (eEF1A) 阻害剤であるテルナチン-4を用いた化学遺伝学的アプローチ.
定量プロテオミクスは,ユビキチン化タンパク質を識別する.
E3リガゼRNF14とRNF25とリボソーム衝突センサーGCN1の役割を調査した.

主要な成果:

テルナチン-4は,停滞したリボソームでeEF1Aのユビキチン化と分解を誘発する.
RNF14とRNF25はeEF1Aの分解に不可欠なE3リガゼである.
GCN1はRNF14をeEF1Aにユビキチナートし,RNF25はRPS27A/eS31にユビキチナートし,二重シグナル入力を提供します.
特定されたeEF1Aおよび特定のリボソームタンパク質のユビキチン化.

結論:

新しいユビキチン信号ネットワークがリボソームA部位をモニターします
このネットワークは,eEF1AとeRF1を含む,停止した変換因子の劣化を促進します.
リボソームの品質管理とプロテオスタシスの維持に関する洞察を提供します.

キーワード:

CRISPRiスクリーン E3リガゼ K6結合ユビキチン RWDドメイン diGly プロテオミクス自然産物タンパク質合成リボソームのユビキチン化リボソーム品質管理変換因子

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