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関連する概念動画

Leaky Scanning02:28

Leaky Scanning

5.8K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.8K
Bacterial Protein Maturation01:26

Bacterial Protein Maturation

679
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
679
Improving Translational Accuracy02:07

Improving Translational Accuracy

15.4K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
15.4K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

11.3K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.3K
Initiation of Translation02:33

Initiation of Translation

40.0K
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...
40.0K
Translational Regulation01:29

Translational Regulation

766
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,...
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Updated: Mar 19, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

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ロカグラートはDEAD-boxタンパク質 eIF4Aをシーケンスを選択するトランスレーション抑制剤に変換する.

Shintaro Iwasaki1, Stephen N Floor1, Nicholas T Ingolia1

  • 1Department of Molecular and Cell Biology, Center for RNA Systems Biology, University of California, Berkeley, California 94720, USA.

Nature
|June 17, 2016
PubMed
まとめ

ロカグラミドA (RocA) は,ユカリオット開始因子4A (eIF4A) を標的として,選択的に癌細胞を殺害する. この薬はeIF4Aを特定のRNA配列に絞り込み,タンパク質の合成を妨害し,癌細胞の発現を減少させます.

科学分野:

  • 分子生物学
  • 生物化学
  • 癌 研究

背景:

  • ロカグラミドA (RocA) はタンパク質合成を阻害し,アヌプロイド腫瘍細胞を選択的に標的とする.
  • RocAは,ATP依存のRNAヘリコースであるエウカリオット開始因子4A (eIF4A) を標的にし,構造化されたmRNA5'未翻訳領域に対する選択性が示唆されている.
  • 以前の仮説では,RocAはeIF4Aの可用性を減少させ,または構造化されたmRNA領域を標的として翻訳を抑制することを示唆していた.

研究 の 目的:

  • RocAが選択的に翻訳を抑制する正確なメカニズムを解明する.
  • RocAの作用メカニズムにおけるmRNA二次構造とeIF4Aの利用可能性の役割を調査する.
  • RocAが特定のメッセンジャーRNAを標的にする際の選択性を決定する.

主な方法:

  • eIF4A- RNAの相互作用を研究するためのインビトロ生化学測定法.
  • 細胞ベースの実験で,翻訳抑制とタンパク質発現を評価する.
  • RocAのeIF4A結合親和性とRNAヘリケース活性に対する影響の分析.

主要な成果:

  • RocAの選択性は主にmRNA 5' 未翻訳領域の二次構造によって決定されません.

さらに関連する動画

Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions
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Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions

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Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells
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Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells

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関連する実験動画

Last Updated: Mar 19, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

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Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions
10:40

Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions

Published on: December 28, 2016

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Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells
14:29

Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells

Published on: December 25, 2021

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  • RocAは,eIF4Aの可用性を低下させることで翻訳を抑制しません.
  • RocAは,eIF4Aをポリプリン配列にATPから独立して固定し,43Sスキャニングを阻害し,早期の翻訳を開始します.
  • 結論:

    • RocAは,eIF4Aとポリプリン配列の間の配列特異的な相互作用を安定させることで,翻訳を選択的に抑制する.
    • このメカニズムは,上流の翻訳開始と標的のトランスクリプトからのタンパク質発現の減少につながります.
    • この研究は,治療効果のための配列選択性RNA-タンパク質相互作用の安定化薬の新しい例を提供します.