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翻訳ダイナミクスにおけるコドン順序の役割
Gina Cannarozzi1, Gina Cannarrozzi, Nicol N Schraudolph
1Institute of Computational Science, ETH Zurich, 8092 Zurich, Switzerland.
Cell
|April 21, 2010
まとめ
遺伝子発現はコドン選択によって影響を受けます. この研究は,細胞が同じ転送RNA (tRNA) を繰り返しアミノ酸に使用することを好むことを明らかにし,翻訳速度に影響を与え,ゲノムシグネチャーを残します.
科学分野:
- 分子生物学は分子生物学である.
- ゲノミクスゲノミクスとは
- バイオフィジックス 生物物理学
背景:
- 遺伝コードは退化しており,複数のコードンが単一のアミノ酸をコードしている.
- コドンの選択は,遺伝子発現レベルに影響することが知られている.
- 同義的なコドン使用の正確なメカニズムとゲノム学的な影響は,依然として研究の活発な分野です.
研究 の 目的:
- 同義的なコドン使用がコード配列内でランダムであるか偏っているかどうかを調査する.
- コドン使用パターンが,転送RNA (tRNA) の利用可能性と使用量と相関するかどうかを判断する.
- コドン相関が翻訳ダイナミクスやゲノムシグネチャーに与える影響を明らかにする.
主な方法:
- S. cerevisiaeのコード配列におけるコドン使用パターンの分析.
- 同義的なコドン発生とその関連するtRNAの相関分析.
- 相関対反相関コドン配列の比較翻訳速度アッセイ.
主要な成果:
- 同義語コードンの使用は非ランダムで,同じアミノ酸の後のコードンは同じtRNAを好む.
- このコドン-tRNA相関は,急速に誘発された遺伝子ではより顕著です.
- コドン相関は,反相関配列と比較して翻訳速度を大幅に加速します.
- 証拠は,より遅いtRNA拡散とリボソームでの潜在的なtRNAチャネリングを示唆しています.
結論:
- 翻訳のダイナミクスは,ゲノム内の有意で非ランダムなサインを残します.
- コドン使用バイアスは,翻訳効率を最適化するために積極的に規制されています.
- リボソーム関連tRNAダイナミクスは,遺伝子発現の調節に重要な役割を果たします.
関連する概念動画
From DNA to Protein
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Leaky Scanning
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 stands for...
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...
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...
Improving Translational Accuracy
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...
Improving Translational Accuracy
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...

