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Improving Translational Accuracy02:07

Improving Translational Accuracy

15.2K
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...
15.2K
Improving Translational Accuracy02:07

Improving Translational Accuracy

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3.7K
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
Translation in Prokaryotes01:29

Translation in Prokaryotes

1.8K
Prokaryote translation is a complex, highly coordinated process that converts genetic information from mRNA into functional proteins. It involves three stages: initiation, elongation, and termination, each facilitated by specific molecular components.Initiation of TranslationThe process begins with the assembly of the ribosomal subunits and initiation factors on the mRNA. In bacteria, the 30S ribosomal subunit recognizes the Shine-Dalgarno sequence in the mRNA, a conserved region upstream of...
1.8K
Point and Frameshift Mutations01:30

Point and Frameshift Mutations

1.3K
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
1.3K
From DNA to Protein03:06

From DNA to Protein

23.1K
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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関連する実験動画

Updated: Feb 19, 2026

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers
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Pichia-CLM:Komagataella phaffiiの言語モデルベースのコドン最適化パイプライン

Harini Narayanan1, J Christopher Love1,2

  • 1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.

Proceedings of the National Academy of Sciences of the United States of America
|February 17, 2026
PubMed
まとめ

科学者たちは,酵母コマガタエラファフィイ (Komagataella phaffii) のタンパク質生産を改善するために,言語モデルを使用した. このコドン使用バイアスの最適化により,タンパク質の生産量は3倍まで増加し,既存のツールを上回った.

キーワード:
バイオテクノロジー バイオテクノロジーコドン使用バイアスエンコーダー・デコーダー・ネットワーク遺伝子配列の遺伝子配列について再結合タンパク質の生産

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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

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Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein
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Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein

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関連する実験動画

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Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers
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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

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Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein
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Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein

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科学分野:

  • バイオテクノロジー バイオテクノロジー
  • コンピュータ生物学 コンピュータ生物学
  • ゲノミクスゲノミクスとは

背景:

  • 同義語コードン使用バイアス (CUB) は,遺伝子発現とタンパク質生産に影響を与えます.
  • 宿主生物,遺伝子機能,コドン位置などの要因は,CUBに影響します.
  • コドン利用の最適化は,効率的な異質タンパク質発現に不可欠です.

研究 の 目的:

  • コドン使用バイアスを学び,適用するための言語モデルベースのパイプラインを開発する.
  • 産業用宿主であるコマガタエラ・ファフィイ (Komagataella phaffii) の異質タンパク質の産生を促進する.
  • 開発されたパイプラインのパフォーマンスを既存のコドン最適化ツールと比較するために.

主な方法:

  • ホストゲノムからコドン使用パターンを学ぶために言語モデルを使用した.
  • Pichia-Codon言語モデル (Pichia-CLM) パイプラインを開発しました.
  • 適用されたPichia-CLMは,K. phaffii.の異質タンパク質発現のための配列を最適化する.
  • タンパク質の生産レベルを評価し,結果を商業的なツールと比較した.

主要な成果:

  • ネイティブ配列と比較して異質タンパク質の生成を最大3倍まで向上させました.
  • Pichia-CLMは,複雑性の異なるタンパク質の生産性を一貫して改善しました.
  • 生成された配列は宿主細胞のタンパク質コドン使用特性を模倣した.
  • 負のシスレギュレータと重複要素を学び,避けることに成功しました.

結論:

  • 言語モデルは,ゲノムデータからコドン使用パターンを効果的に学習できます.
  • Pichia-CLMは,コドン最適化のための堅牢で効率的な方法を提供します.
  • このアプローチは,産業用バイオテクノロジーにおける異質タンパク質の生産を改善するための大きな可能性を秘めています.