翻译启动的分子基础及其在真核细胞中的调节
Jailson Brito Querido1,2,3, Irene Díaz-López1, V Ramakrishnan4
1MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
Nature reviews. Molecular cell biology
|December 5, 2023
概括
基因表达的调节至关重要. 转录后控制,特别是翻译启动,对于细胞功能和治疗发展至关重要,最近的研究澄清了其复杂的机制.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 基因表达调节对生命至关重要.
- 包括翻译在内的转录后调节与转录调节同样重要.
- 翻译启动是一个关键的控制点,但其机制尚未完全理解.
研究的目的:
- 审查目前对真核细胞翻译启动的理解.
- 突出最近翻译启动机制的进展.
- 讨论翻译启动在健康和疾病中的作用.
主要方法:
- 评论最近的科学文献.
- 专注于组装43S预启动复合体.
- 对真核细胞翻译启动因子4F (eIF4F) 招募和核糖体扫描的分析.
主要成果:
- 最近的研究已经阐明了以前不清楚的翻译启动方面.
- 了解43S预启动复合体的组装已经取得了进展.
- 已经获得了对核糖体扫描和启动密码体选择的洞察力.
结论:
- 细胞翻译启动是一个复杂的过程,具有关键的调节作用.
- 在理解翻译启动方面取得的进展为创新疗法提供了潜力.
- 对翻译启动机制的进一步研究对于健康和疾病洞察至关重要.
相关概念视频
Initiation of Translation
33.6K
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...
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...
33.6K
Improving Translational Accuracy
11.1K
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...
11.1K
Regulation of Expression at Multiple Steps
917
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...
917
Regulation of Expression Occurs at Multiple Steps
22.7K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.7K
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
Translation
14.9K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
14.9K


