人类eIF4F识别mRNA帽的动力学和调节
Hea Jin Hong1, Matthew G Guevara1, Siyu Li2
1Department of Biochemistry, University of California Riverside, Riverside, CA 92521.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
人体翻译启动因子4F (eIF4F) 复杂的动态表明,eIF4G调节了eIF4E-mRNA结合,而eIF4A缓解了这种抑制,以实现高效的翻译. 这揭示了eIF4G的新监管作用.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 细胞翻译启动对于基因表达至关重要,并受到启动因子4F (eIF4F) 复合体的严格调节.
- eIF4F复合体 (eIF4E,eIF4G和eIF4A) 结合了mRNA的5'盖,促进了核糖体的招募.
- 人类eIF4F-mRNA相互作用的精确动态仍然不太清楚,这限制了对翻译调节的机制性见解.
研究的目的:
- 在mRNA帽识别过程中调查人类eIF4F复合体内的动态相互作用.
- 阐明个人eIF4F子单位在调节翻译启动中的作用.
- 了解上限依赖的翻译法规的机制基础.
主要方法:
- 单分子光试验可实时可视化eIF4E-mRNA盖结合.
- 生物化学试验用于研究eIF4F复合体内的子单元相互作用.
- 分子动力学模拟用于模拟静电相互作用和结合动力学.
主要成果:
- 人类eIF4G,特别是它的C端,抑制了eIF4E与mRNA的暂时结合.
- 结合核酸的eIF4A减轻了这种压制,作为有效的顶部识别的关键决定因素.
- eIF4G通过静电相互作用调节eIF4E-mRNA相互作用频率,揭示其作为速度限制因素的作用.
- 单独的内在eIF4F-mRNA动力学不足以进行连接式核糖体扫描.
结论:
- 人类eIF4G在控制eIF4F的mRNA帽子识别方面发挥着意想不到的中央监管作用.
- eIF4A对于克服eIF4G中介的压制至关重要,从而促进有效的翻译启动.
- 人类和酵母eIF4F复合体之间的mRNA识别机制和子单元作用存在显著差异.
- 这些发现提供了对真核细胞翻译启动调节的基本见解.
相关概念视频
02:24Regulation of Expression Occurs at Multiple Steps
23.5K
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...
23.5K
01:35Pre-mRNA Processing: Modification of pre-mRNA Ends
9.9K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
9.9K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.2K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.2K
01:23Regulation of Expression at Multiple Steps
1.0K
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...
1.0K
02:01pre-mRNA Processing
53.6K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
53.6K
02:51mRNA Stability and Gene Expression
5.7K
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
Cis-acting Elements involved in mRNA stability
5.7K