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相关概念视频

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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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...
9.9K
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
Transcription Elongation Factors02:35

Transcription Elongation Factors

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Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
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Regulated mRNA Transport02:22

Regulated mRNA Transport

6.3K
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...
6.3K
Termination of Translation01:44

Termination of Translation

25.3K
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
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相关实验视频

Updated: Jun 20, 2025

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
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eIF1和eIF5动态控制翻译开始站点保真

Rosslyn Grosely1, Carlos Alvarado1, Ivaylo P Ivanov2

  • 1Dept. of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.

bioRxiv : the preprint server for biology
|July 19, 2024
PubMed
概括

细胞启动因子eIF1和eIF5协调蛋白质合成开始地点的选择. 它们独特的结合动态确保了准确的翻译启动,防止了蛋白质身份和功能的错误.

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科学领域:

  • 分子生物学分子生物学
  • 细胞生物学 细胞生物学
  • 生物化学 生物化学

背景情况:

  • 翻译启动对于蛋白质合成至关重要,并且受到严格监管.
  • 翻译启动的失调与各种人类疾病有关.
  • 细胞启动因子 (eIFs),包括eIF1和eIF5,在开始地点选择中发挥关键作用.

研究的目的:

  • 研究eIF1和eIF5在人类翻译启动过程中的实时功能.
  • 阐明eIF1和eIF5在确保准确的开始地点选择方面的作用.
  • 了解eIF1和eIF5动态是如何被RNA序列和细胞水平调节的.

主要方法:

  • 单分子光分析在体外复制的人类翻译启动.
  • 实时监测eIF1和eIF5对信使RNA的结合动态.
  • 在纤维化分析中,包括eIF1和eIF5.5的淘汰和过度表达.

主要成果:

  • eIF1离开43S启动复合体是快速的,并取决于启动地点,因替代地点或更长的5'UTR而造成延迟.
  • eIF1动态采样启动复合体,在替代启动地点进行长时间采样.
  • eIF5在启动晚期暂时结合,需要一个启动位点,并通过替代位点抑制.

结论:

  • eIF1和eIF5在翻译启动中表现出对立的角色,控制开始站点选择的准确性.
  • eIF1和eIF5的多个绑定事件精确地调节了开始位置的准确性.
  • 根据细胞条件,微调eIF1和eIF5水平的翻译启动忠实度.