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相关概念视频

From DNA to Protein03:06

From DNA to Protein

18.1K
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...
18.1K
Leaky Scanning02:28

Leaky Scanning

5.1K
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...
5.1K
The Central Dogma01:25

The Central Dogma

124.2K
Overview
124.2K
Initiation of Translation02:33

Initiation of Translation

31.6K
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...
31.6K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

10.6K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.6K
tRNA Activation02:26

tRNA Activation

19.1K
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
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相关实验视频

Updated: Jun 12, 2025

Residue-specific Incorporation of Noncanonical Amino Acids into Model Proteins Using an Escherichia coli Cell-free Transcription-translation System
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Residue-specific Incorporation of Noncanonical Amino Acids into Model Proteins Using an Escherichia coli Cell-free Transcription-translation System

Published on: August 1, 2016

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一种生成语言模型解码了mRNA设计的编码子选择的上下文约束.

Marjan Faizi, Helen Sakharova, Liana F Lareau

    bioRxiv : the preprint server for biology
    |June 4, 2025
    PubMed
    概括

    一个新的语言模型Trias通过从数据中学习复杂的编码子使用规则来优化合成mRNA序列. 它提高了mRNA稳定性和蛋白质输出,优于现有的工具.

    科学领域:

    • 计算生物学和生物信息学
    • 分子生物学和遗传学
    • 合成生物学 合成生物学

    背景情况:

    • 遗传密码的退化允许同名的编码子,在蛋白质编码基因中产生序列多样性.
    • 子的选择影响mRNA功能和蛋白质的产生,这对于推进mRNA技术至关重要.
    • 现有的编码子优化方法无法捕捉编码子使用中的复杂上下文模式.

    研究的目的:

    • 开发一种新的语言模型,Trias,用于理解和预测上下文依赖的代码子使用.
    • 为了生成符合生物约束的特定物种的编码子序列,并提高mRNA性能.
    • 为优化合成mRNA设计提供数据驱动的框架.

    主要方法:

    • 在数以百万计的真核生物编码序列上训练了一个编码解码语言模型 (Trias).
    • 在序列数据中整合了本地和全球依赖关系,以学习codon使用规则.
    • 评估了Trias产生的序列与mRNA稳定性,核糖体负载和蛋白质输出的实验测量.

    主要成果:

    • 在没有明确的蛋白质表达训练的情况下,Trias学会了复杂的编码子使用模式.
    • 来自Trias的生成序列和得分与mRNA稳定性和蛋白质输出的实验测量有很强的相关性.

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    Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers
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    Residue-specific Incorporation of Noncanonical Amino Acids into Model Proteins Using an Escherichia coli Cell-free Transcription-translation System
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    Measurement of Specific Mycobacterial Mistranslation Rates with Gain-of-function Reporter Systems
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    Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers
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    Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

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  • 在产生高表达性编码子序列变异方面,Trias在商业编码子优化工具上表现出色.
  • 结论:

    • 特里亚斯为合成mRNA设计的编码子优化提供了一种强大的数据驱动的方法.
    • 该模型提供了对控制子选择的分子和进化原理的见解.
    • 这一框架推进了合成mRNA的设计,提高了稳定性和蛋白质表达.