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Translation01:31

Translation

157.1K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
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Translation01:31

Translation

17.9K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
17.9K
Initiation of Translation02:33

Initiation of Translation

39.1K
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...
39.1K
Improving Translational Accuracy02:07

Improving Translational Accuracy

15.0K
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...
15.0K
Termination of Translation01:44

Termination of Translation

27.8K
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
27.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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コドン特異的な翻訳再プログラミングは,標的治療に対する耐性を促進する.

Francesca Rapino1,2, Sylvain Delaunay1,2, Florian Rambow3,4

  • 1Laboratory of Cancer Signaling, University of Liège, Liège, Belgium.

Nature
|June 22, 2018
PubMed
まとめ

振動性tRNA改変酵素は,メラノーマ細胞の生存と薬剤耐性にとって極めて重要です. これらの酵素の抑制は MAPK信号伝達とともに メラノーマの有望な治療策となります

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Plant Promoter Analysis: Identification and Characterization of Root Nodule Specific Promoter in the Common Bean
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Plant Promoter Analysis: Identification and Characterization of Root Nodule Specific Promoter in the Common Bean

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関連する実験動画

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科学分野:

  • 分子生物学
  • 腫瘍学
  • 生物化学

背景:

  • mRNAの翻訳再プログラミングは,がんの発生と薬剤耐性に関連しています.
  • 翻訳再プログラムに 基づく正確な分子メカニズムは 未知のままです
  • タンパク質合成中の正確なコドン解読には,振動型tRNAの改変が不可欠である.

研究 の 目的:

  • BRAF V600E誘発性メラノーマにおけるバブルウリジン34 (U34) tRNA修飾酵素の役割を調査する.
  • MAPK阻害剤に対する治療抵抗に対するU34酵素の関与を調査する.
  • U34酵素,タンパク質合成,メラノーマ細胞生存のメカニズム的関連を解明する.

主な方法:

  • BRAF V600EメラノーマモデルにおけるU34酵素発現の分析
  • MAPKシグナル伝達とU34酵素の同時抑制による細胞活性の評価 (ELP3,CTU1,CTU2).
  • PI3K経路の活性化とそのU34酵素発現への影響の調査
  • HIF1A mRNAトランスレーションとHIF1αタンパク質の酵素媒介による調節の検討.

主要な成果:

  • BRAF V600E メラノーマ細胞は U34酵素に依存して生存しています.
  • MAPKシグナル伝達とU34酵素の結合阻害は,シネージ的細胞毒性を示しています.
  • 抵抗メカニズムであるPI3K経路の活性化により,U34酵素の発現が著しく上昇する.
  • U34酵素は,HIF1Aの翻訳を調節し,HIF1αタンパク質のレベルを維持することによって,メラノーマの糖分分解を促進します.

結論:

  • U34酵素は,BRAF V600Eメラノーマにおけるタンパク質合成の再配線の重要な媒介者である.
  • MAPK阻害剤と併用して,U34酵素を標的とした治療は,メラノーマに対する潜在的な治療戦略です.
  • 高濃度のU34酵素とHIF1αは,抗BRAF治療に対する得られた耐性に関連しており,メラノーマ細胞生存と治療耐性を促進する役割を強調しています.