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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

3.7K
3.7K
Leaky Scanning02:28

Leaky Scanning

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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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相关实验视频

Updated: Feb 19, 2026

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers
10:41

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

Published on: June 24, 2019

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皮奇亚-CLM:基于Komagataella phaffii的语言模型的编码子优化管道.

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
概括

科学家们使用语言模型来改善酵母 Komagataella phaffii.酵母中的蛋白质生产. 这种编码子使用偏差优化增强了蛋白质产量高达三倍,超过了现有的工具.

关键词:
生物技术是生物技术.codon 使用偏差编码器解码器网络基因序列的基因序列是什么再组合蛋白质的生产.

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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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相关实验视频

Last Updated: Feb 19, 2026

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers
10:41

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

Published on: June 24, 2019

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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

Published on: February 18, 2022

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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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科学领域:

  • 生物技术是生物技术.
  • 计算生物学 计算生物学
  • 基因组学就是基因组学.

背景情况:

  • 同义符号使用偏差 (CUB) 影响基因表达和蛋白质生产.
  • 诸如宿主生物体,基因功能和代码子位置等因素会影响CUB.
  • 优化编码子使用对于高效的异质蛋白表达至关重要.

研究的目的:

  • 开发一种基于语言模型的管道,用于学习和应用codon使用偏差.
  • 增强工业宿主 Komagataella phaffii.中异质蛋白质的产生.
  • 将开发管道的性能与现有的编码子优化工具进行比较.

主要方法:

  • 利用语言模型从宿主基因组中学习编码子使用模式.
  • 开发了Pichia-Codon语言模型 (Pichia-CLM) 管道.
  • 应用了Pichia-CLM来优化K. phaffii中异质蛋白表达的序列.
  • 评估蛋白质生产水平,并将结果与商业工具进行比较.

主要成果:

  • 与原生序列相比,异质蛋白质生产达到三倍的增强.
  • 皮奇亚-CLM持续提高了不同复杂度的蛋白质的生产率.
  • 生成的序列模仿了宿主细胞蛋白质的使用特性.
  • 成功学习并避免负面的 cis-regulatory 和重复元素.

结论:

  • 语言模型可以有效地从基因组数据中学习代码的使用模式.
  • 皮奇亚-CLM提供了一种强大而高效的编码子优化方法.
  • 这种方法具有显著的潜力,可以改善工业生物技术中的异质蛋白质生产.