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相关概念视频

Improving Translational Accuracy02:07

Improving Translational Accuracy

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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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Initiation of Translation02:33

Initiation of Translation

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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...
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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...
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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Regulated mRNA Transport02:22

Regulated mRNA Transport

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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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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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相关实验视频

Updated: Jun 1, 2025

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
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通过合理的5'UTR和3'UTR组合设计优化mRNA翻译效率.

Ting Li1, Gangfeng Liu2, Guolong Bu1

  • 1State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Gene
|January 17, 2025
PubMed
概括

研究人员通过设计新的未翻译区域 (UTR) 来优化信使RNA (mRNA) 疗法. 结合特定的5'UTR和3'UTR序列,显著提高了用于增强mRNA治疗的蛋白质生产.

关键词:
3",UTR"可以使用.5′UTR 5′UTR是指UTR的时间.翻译效率 翻译效率 翻译效率这是一种UTR组合.它们是mRNARNA.

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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
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Quantitative Immunofluorescence to Measure Global Localized Translation
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科学领域:

  • 分子医学是分子医学.
  • 生物技术是生物技术.
  • 基因工程是一种基因工程.

背景情况:

  • 基于信使RNA (mRNA) 的疗法显示出治疗疾病的潜力,但面临着低翻译效率和短半衰期等挑战.
  • 未翻译区域 (UTR) 关键调节mRNA稳定性和翻译效率,使它们成为优化的主要目标.

研究的目的:

  • 通过5'UTRs的新设计和3'UTRs的组合选来提高外源mRNA翻译效率.
  • 确定新的UTR序列和组合,以改善mRNA治疗的蛋白质表达.

主要方法:

  • 使用组合查策略来设计和测试新型5'UTR与各种3'UTR结合使用.
  • 设计了一种新的5'UTR,被指定为5UTR05,其性能与参考mRNA-1273 5'UTR.相比.
  • 查发现了5UTR05与特定的3'UTR结合时产生的协同效应,包括来自免疫球蛋白重常数玛2 (IGHG2) 和线粒体编码的12S核糖体RNA (mtRNR1) 的效应.

主要成果:

  • 这种新型5UTR05的蛋白质表达水平与高性能mRNA-1273 5'UTR.R.相当.
  • 与使用单个3'UTR相比,将5UTR05与IGHG2和mtRNR1 3'UTR结合起来显著提高了mRNA翻译效率.
  • 这种协同作用的组合导致了优越的蛋白质表达,突出了特定的UTR配对的重要性.

结论:

  • 新的UTR设计和组合策略可以有效地克服外源mRNA翻译效率的局限性.
  • 已确定的协同UTR组合 (5UTR05与IGHG2和mtRNR1 3'UTRs) 为开发先进的mRNA疗法提供了一个有前途的方法.
  • 对UTR组合的进一步探索可以导致定制的mRNA结构,用于各种治疗应用的最佳表达.