タンパク質合成装置の酸素調節スイッチ
James Uniacke1, Chet E Holterman, Gabriel Lachance
1Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Nature
|June 9, 2012
まとめ
細胞は酸素が不足したときにタンパク質を合成し,新しい複合体を形成します. HIF-2α,RBM4,eIF4E2を含むこの複合体は,正常なキャップ結合阻害を回避して翻訳を可能にします.
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
- バイオケミストリー バイオケミストリー
背景:
- タンパク質合成は生命にとって極めて重要で,真核細胞のトランスレーション開始因子4E (eIF4E) がmRNAキャップに結合することで開始される.
- 低酸素 (低酸素) は,ラパミシン (mTOR) に依存する経路の哺乳類の標的経由によるキャップ媒介翻訳を阻害し,eIF4E.を隔離します.
- 内部リボソームエントリーサイト (IRES) のような代替翻訳メカニズムは,低酸素下でのタンパク質合成を説明するのに不十分です.
研究 の 目的:
- 酸素不足とeIF4E阻害の条件下で細胞がタンパク質を合成する方法を調査する.
- 新規の酸素調節型トランスレーション開始メカニズムを特定する.
- 低酸素誘発型トランスレーション複合体の構成要素と機能を特徴づけるために.
主な方法:
- 酸素調節型トランスレーション開始複合体の形成と特徴.
- 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) を利用してRNA要素を特定する.
- 複合体のメッセンジャーRNA (mRNA) への募集を分析する.
主要な成果:
- 低酸素症は,低酸素症誘導因子2α (HIF-2α),RNA結合タンパク質RBM4およびeIF4E2.2.を含む新しい複合体の形成を刺激する.
- PAR-CLIPは,この複合体を特定のmRNAに勧誘するRNA低酸素反応要素 (rHRE) を特定した.
- HIF-2α-RBM4-eIF4E2複合体は,mRNAキャップをrHREに結合させ,キャップ依存の翻訳を可能にし,低酸素誘発の抑圧を克服します.
結論:
- 細胞は,コア翻訳機構をスイッチする酸素調節プログラムを持っています.
- 新しく発見されたHIF-2α,RBM4,eIF4E2を含む複合体は,低酸素期における選択的キャップ依存タンパク質合成を媒介する.
- このメカニズムは,酸素不足とeIF4E阻害にもかかわらず,細胞が翻訳能力を維持することを可能にします.
関連する概念動画
Types of RNA
61.4K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
61.4K
Riboswitches
8.0K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.0K
Types of RNA
13.9K
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
RNA Performs Diverse...
13.9K
Transcriptional Regulation: Riboswitches
1.2K
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
1.2K
Translational Regulation
893
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
893
Stringent Response in E. coli
533
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
533


