TTC5はmRNAの分解を通じてチューブリンを自己調節する
Zhewang Lin1, Ivana Gasic2, Viswanathan Chandrasekaran1
1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Science (New York, N.Y.)
|November 16, 2019
まとめ
テトラトリコペプチドタンパク質5 (TTC5) は,チューブリンが豊富であるときにチューブリンメッセンジャーRNA (mRNA) を分解してチューブリンレベルを調節する. この発見は タンパク質濃度と細胞分裂の精度を制御する 新しいメカニズムを明らかにしています
科学分野:
- 分子生物学
- 細胞生物学
- 生物化学
背景:
- チューブリンとは,細胞分裂,細胞内輸送,細胞の形状の維持に不可欠な細胞骨格タンパク質である.
- 細胞のチューブリン濃度は,メッセンジャーRNA (mRNA) 降解を含むフィードバックメカニズムによって厳しく調節されるが,正確なメカニズムは不明である.
研究 の 目的:
- mRNAの分解によるチューブリン濃度の自己調節に起因する未知の因子を特定する.
- 細胞のチューブリンに反応してチューブリンmRNA濃度が制御されるメカニズムを解明する.
主な方法:
- チューブリン特異のリボソーム関連因子の特定
- タンパク質-RNAとタンパク質の相互作用を分析する生化学的測定法
- クリオ電子顕微鏡を用いた構造分析
- TTC5の遺伝子操作とチューブリン自己調節とミトスフィデリティの評価
主要な成果:
- テトラテトリコペプチドタンパク質5 (TTC5) は,リボソームと新生チューブリンポリペプチドに結合する重要な因子として特定されました.
- TTC5は,溶解性チューブリン濃度が高いとき,チューブリンmRNAのコトランスレーション分解を促進する.
- リボソームまたは新生チューブリン結合を妨害するTTC5の変異は,チューブリン自己調節を廃止し,ミトーシス中の染色体分離エラーにつながります.
結論:
- TTC5は新生チューブリン合成とmRNAの分解を結び,チューブリンホメオスタシスを調節する特異性因子として作用する.
- このメカニズムは,細胞分裂中の正確な染色体分離に不可欠なチューブリンレベルを正確に制御します.
- 発見は,新生ポリペプチド認識によって媒介される標的型mRNAの分解のための新しい経路を明らかにします.
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