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相关概念视频

mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
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RNA Stability01:53

RNA Stability

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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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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...
5.2K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
Initiation of Translation02:33

Initiation of Translation

34.3K
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...
34.3K
Improving Translational Accuracy02:07

Improving Translational Accuracy

11.7K
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...
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相关实验视频

Updated: Jul 31, 2025

An Oligonucleotide-based Tandem RNA Isolation Procedure to Recover Eukaryotic mRNA-Protein Complexes
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An Oligonucleotide-based Tandem RNA Isolation Procedure to Recover Eukaryotic mRNA-Protein Complexes

Published on: August 18, 2018

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优化mRNA设计的算法提高了稳定性和免疫性

He Zhang1,2, Liang Zhang1,2,3, Ang Lin4,3

  • 1Baidu Research USA, Sunnyvale, CA, USA.

Nature
|May 2, 2023
PubMed
概括
此摘要是机器生成的。

新的线性设计算法优化传递 RNA (mRNA) 疫苗序列的稳定性和蛋白质表达. 这一突破显著提高了抗体的产生,克服了当前mRNA疫苗技术的关键局限性.

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Synthesis and Characterization of mRNA-Loaded PolyBeta Aminoesters Nanoparticles for Vaccination Purposes
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相关实验视频

Last Updated: Jul 31, 2025

An Oligonucleotide-based Tandem RNA Isolation Procedure to Recover Eukaryotic mRNA-Protein Complexes
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An Oligonucleotide-based Tandem RNA Isolation Procedure to Recover Eukaryotic mRNA-Protein Complexes

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Synthesis and Characterization of mRNA-Loaded PolyBeta Aminoesters Nanoparticles for Vaccination Purposes
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Synthesis and Characterization of mRNA-Loaded PolyBeta Aminoesters Nanoparticles for Vaccination Purposes

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Using Lipid Nanoparticles for the Delivery of Chemically Modified mRNA into Mammalian Cells
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Using Lipid Nanoparticles for the Delivery of Chemically Modified mRNA into Mammalian Cells

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科学领域:

  • 生物技术
  • 计算生物学
  • 疫苗学

背景情况:

  • 使者RNA (mRNA) 疫苗对抗COVID-19至关重要,但由于mRNA的不稳定性和退化而面临挑战.
  • 这些局限性阻碍了疫苗的储存,分发和整体疗效.
  • 增强mRNA二次结构和子优化是改善稳定性和蛋白质表达的关键.

研究的目的:

  • 开发一个以原则为基础的mRNA设计算法,优化结构稳定性和子使用.
  • 解决像SARS-CoV-2尖端蛋白这样的复杂目标的mRNA设计空间的计算限制.

主要方法:

  • 利用计算语言学中的格子解析概念创建了线性设计算法.
  • 线性设计同时优化了mRNA稳定性和子使用.
  • 应用该算法来设计SARS-CoV-2尖端蛋白的mRNA序列.

主要成果:

  • 线性设计在11分钟内发现了最佳mRNA设计.
  • 设计的mRNA显著改善了半衰期和蛋白质表达.
  • 在小鼠中,与COVID-19和水病毒mRNA疫苗的代码优化基准相比,抗体标量增加了128倍.

结论:

  • 线性设计为优化mRNA序列提供了一个计算可行的解决方案.
  • 这种方法显著提高mRNA疫苗的疗效和稳定性.
  • 这种方法对开发下一代基于mRNA的疗法,包括癌症和其他疾病的疫苗和治疗有很大的潜力.