Rli1/ABCE1は,リボソームの終了をリサイクルし,3'UTRにおける翻訳再起動を制御する
David J Young1, Nicholas R Guydosh2, Fan Zhang1
1Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|August 16, 2015
まとめ
エッセンシャルタンパク質Rli1 (ABCE1) は細胞内のリボソームリサイクルに不可欠です. 十分なRli1がなければ,リボソームはmRNAで停止し,望ましくない3'UTR翻訳につながり,タンパク質の恒常性に影響を与えます.
科学分野:
- 分子生物学
- 細胞生物学
- 遺伝学
背景:
- リボソームのリサイクルは,タンパク質合成ホメオスタシスの重要なプロセスです.
- Rli1として知られるABCE1タンパク質は,細胞のプロセスに役割を果たします.
- リボソームの動態を理解するには,Rli1の in vivo 機能を理解することが不可欠です.
研究 の 目的:
- リボソームのリサイクルにおけるRli1/ABCE1のインビボ機能を調査する.
- リボソームの分布と翻訳に対する Rli1 枯渇の影響を特徴づける.
- Rli1 と Dom34 のような他のリボソーム救済因子の相互作用を解明する.
主な方法:
- リボソームプロファイリングは,mRNAにおけるリボソーム占有率を分析する.
- タンパク質の機能と相互作用を評価する生化学的測定法
- ウエスタン・ブロット分析と質量スペクトロメトリーでペプチド合成を確認
主要な成果:
- 減少したRli1レベルは,ストップコドンと3'UTRで80Sリボソームの蓄積を引き起こします.
- 停止したリボソームは3'UTRの翻訳を再開し,小さなペプチドを生成する.
- リボソーム救済因子Dom34は,Rli1が枯渇すると,リサイクルされていないリボソームを大幅にクリアします.
- 3'UTR翻訳は野生型の細胞で観察され,ストレス条件下で増加します.
結論:
- Rli1はリボソームの効率的なリサイクルに不可欠であり,リボソームのホメオスタシスを維持します.
- リボソームのリサイクルと再起動の調節は,環境ストレスに対する細胞の反応です.
- この研究は,Rli1媒介のリボソーム品質制御の新しいメカニズムと,細胞適応への影響を明らかにしています.
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