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構造化されたmRNAは,リボソームのプラットフォームに結合することによって,翻訳開始を調節する
Stefano Marzi1, Alexander G Myasnikov, Alexander Serganov
1IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Department of Structural Biology and Genomics, Illkirch, F-67404 France.
Cell
|September 25, 2007
まとめ
メッセンジャーRNA (mRNA) の規制要素は,タンパク質合成を停止することによって遺伝子発現を制御することができます. クリオ電子顕微鏡では,mRNA構造がリボソームからブロックされ,その後解放され,トランスレーションを調節する方法を視覚化しました.
科学分野:
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
- 遺伝学 遺伝学とは
背景:
- 遺伝子発現は,複数のレベルで厳格に規制されています.
- 翻訳開始は遺伝子発現の重要なコントロールポイントです.
- メッセンジャーRNA (mRNA) の5'未翻訳領域 (5'UTR) 内の規制要素は,翻訳開始に影響を与える可能性があります.
研究 の 目的:
- 5' UTR mRNA要素が翻訳開始を調節する構造的メカニズムを視覚化します.
- 抑制タンパク質がmRNAとリボソームと相互作用して翻訳を制御する方法を理解する.
- 規制mRNA要素のためのリボソーム上の潜在的な普遍的結合部位を特定する.
主な方法:
- クリオ電子顕微鏡 (cryo-EM) を使用して,リボソーム複合体のスナップショットを撮影しました.
- リボソーム複合体は,停止状態 (抑制状態) と活性状態 (展開されたmRNA) の両方で視覚化されました.
- 比較的な構造と配列分析が行われました.
主要な成果:
- Cryo-EMは,抑制タンパク質S15に結合した折りたたまれたmRNA構造が,スタートコドンがP部位にアクセスするのを防ぐことでリボソームをブロックする方法を明らかにしました.
- 抑制剤が放出されると,mRNAは展開され,リボソームのmRNAチャネルに入り,翻訳を開始します.
- リボソームの保存された"30Sプラットフォーム"は,5'-mRNA要素を結合させるための普遍的な場所として提案されています.
結論:
- 調節性5' UTR mRNA構造はリボソームを一時的に停止させ,遺伝子発現制御のメカニズムを提供する.
- リボソームは,トランスレーション前始動中にこれらのmRNA構造を収容し,制御するための専用のプラットフォームを有しています.
- このメカニズムは,転写後の遺伝子調節のための保存された戦略を強調しています.
関連する概念動画
Initiation of Translation
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Riboswitches
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...
Initiation of Translation
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Translational Regulation
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,...

