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小型非コーディング・ヴォルトRNA1-1は,オートファギーのリボレギュレータとして作用する
Rastislav Horos1, Magdalena Büscher1, Rozemarijn Kleinendorst1
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Cell
|February 19, 2019
まとめ
ヴォルトRNAs (vtRNAs) は,選択的オートファジーを調節するオートファジー受容体p62に直接結合する. このRNAとタンパク質の相互作用はp62を制御する.
科学分野:
- 分子生物学
- 細胞生物学
- RNA 生物学
背景:
- ヴォルトRNA (vtRNA) は,分子機能がはっきりしない小さな非コーディングRNAである.
- vtRNAは薬剤耐性,アポトーシス,ウイルス複製に関与している.
- 細胞プロセスにおけるvtRNAの正確な役割は,ほとんど不明である.
研究 の 目的:
- 細胞の調節におけるヴォルトRNAの分子機能を調査する.
- ヴォルトRNAとオートファギー受容体p62の相互作用を決定する.
- vtRNAsがオートファギーを調節するメカニズムを解明する.
主な方法:
- vtRNA-p62結合を検出するための共免疫降水測定法
- LNAを用いたvtRNA1-1の過剰発現とノックダウン研究.
- 細胞の飢餓実験で 自動食流を評価する
- vtRNA結合が損なわれたp62変異体の分析
主要な成果:
- ヴォルトRNAは,ヒトおよびマウインの細胞のオートファギー受容体シーケストソーム-1/p62に直接結合する.
- vtRNA1- 1の過剰発現はp62- 依存の自殺を阻害し,ノックダウンはそれを強化する.
- 細胞飢餓はvtRNA1-1のレベルを低下させ,オートファギーを誘発する.
- vtRNAを結合できないp62変異体はホモオリゴメリゼーションとオートファージ効果因子の相互作用が増加している.
結論:
- vtRNA1-1は,p62と結合し,そのオリゴメリゼーションを調節することによって,選択的自を直接調節する.
- この研究は,RNA媒介のタンパク質機能制御の新しいメカニズムを明らかにしています.
- ヴォルトRNAは,選択的自己消化のための新しい種類のレギュレータを表しています.
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