FXR1とArgonaute 2による翻訳のAU-rich-element-mediatedアップレギュレーションが実施されている
Shobha Vasudevan1, Joan A Steitz
1Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA.
Cell
|March 27, 2007
まとめ
AU豊富な元素 (AREs) は遺伝子発現を調節する. 研究者らは,脆弱なX-メンタル遅延関連タンパク質1 (FXR1) とアルゴナウト2 (AGO2) が,細胞成長停止中にAREを含むmRNAの翻訳を活性化することを発見した.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- トランスクリプション後のコントロール
背景:
- mRNA 3'-UTRsのAU豊富な元素 (AREs) は,mRNAの安定性と翻訳の重要なレギュレータである.
- AREsは遺伝子発現に影響を与え,臨床および発達に重大な影響を及ぼします.
- TNFalpha AREは,血清飢餓誘発細胞サイクル停止中に特異的に翻訳を強化する.
研究 の 目的:
- 翻訳活性化の条件下で,AREsに関連するタンパク質を識別する.
- ARE媒介による翻訳制御における特定されたタンパク質の役割を調査する.
- AREシグナル伝達とマイクロRNPに関連するタンパク質の相互作用を解明する.
主な方法:
- in vivoのクロスリンク結合による親和性浄化方法の開発.
- ベースおよび活性化トランスレーション条件下でのARE関連複合体の分離と分析.
- タンパク質機能を評価するためのテザリングアッセイとshRNAノックダウン実験.
主要な成果:
- Fragile-X-mental-retardation-related protein 1 (FXR1) とArgonaute 2 (AGO2) は,新しいARE結合タンパク質として特定されました.
- FXR1とAGO2は,翻訳アクティベーション時にのみAREと関連付けられます.
- 直接的な証拠は,FXR1とAGO2の翻訳活性化機能を確認し,それらの相互依存性を強調しました.
結論:
- FXR1とAGO2は,AREを含むmRNAの細胞成長に依存した翻訳活性化において重要な役割を果たします.
- この発見は,ARE媒介のシグナル伝達とマイクロRNP関連の規制システムとの間の新しいつながりを明らかにしています.
- この研究は,転写後の遺伝子調節を制御する複雑なメカニズムに関する新しい洞察を提供します.
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