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eIF3は,細胞増殖メッセンジャーRNAを標的とし,トランスレーションの活性化や抑制を図る
Amy S Y Lee1, Philip J Kranzusch2, Jamie H D Cate3
11] Department of Molecular &Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Center for RNA Systems Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Nature
|April 8, 2015
まとめ
ユカリオット初期化因子3 (eIF3) は,特定のメッセンジャーRNAを結合することによって,タンパク質合成を制御する. 細胞の成長に不可欠なこの相互作用は,翻訳を活性化または抑制し,がんに対する新しい治療標的を提供することができます.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- タンパク質合成の調節は,発達とストレス反応を含む真核細胞の細胞プロセスにとって不可欠です.
- 13つの亜単位のエウカリオット開始因子3 (eIF3) 複合体は,タンパク質翻訳を開始するために不可欠です.
- eIF3の規制緩和は癌や発達異常と関連しているが,その特定のmRNA標的と規制メカニズムは不明である.
研究 の 目的:
- ゲノム全体でeIF3と相互作用するヒトのトランスクリプトを特定するために.
- eIF3が特定のmRNAの翻訳を調節するメカニズムを解明する.
- 細胞プロセスとがん発生におけるeIF3-mRNA相互作用の影響を調査する.
主な方法:
- eIF3-RNAの相互作用をマッピングするために,光活性化リボヌクレオシド強化クロスリンクと免疫プレシピテーション (PAR-CLIP).
- 特定のmRNAに結合するeIF3の機能分析 (c-JUN,BTG1).
- 翻訳制御のためのRNA幹ループ結合モードの調査.
主要な成果:
- eIF3に結合する特定のmRNAの全ゲノム識別,主に5'未翻訳領域.
- eIF3は,細胞サイクル,分化,アポトーシスを含む細胞成長制御に関与するmRNAを標的にします.
- eIF3は,異なるRNA幹回路結合モードを利用して,c-JUNとBTG1の翻訳を差異的に調節し,アクティベーターとレプレッサーの両方として作用します.
結論:
- eIF3は,直接的なmRNA結合を通じて,遺伝子発現の専門的なレパートリーを管理します.
- 翻訳の活性化と抑制におけるeIF3の二重な役割は,その複雑な規制機能を強調しています.
- eIF3-mRNAの相互作用をターゲットにすることは,発癌を制御するための潜在的な戦略です.
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