人类eIF2A在HeLa细胞的翻译启动和uORF介导的翻译控制中发挥的作用很小
Mykola Roiuk1,2,3, Marilena Neff1,2,3, Aurelio A Teleman1,2,3
1German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
eLife
|July 2, 2025
概括
细胞翻译启动因子eIF2A似乎在翻译启动中没有作用,即使在压力条件下也是如此. 需要进一步的研究来澄清其在RNA生物学中的功能.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 在真核生物中,翻译启动涉及40S核糖体,启动tRNA和三元复合体 (eIF2-GTP-启动tRNA).
- 由于核糖体结合和与eIF4E等因子的相互作用,eIF2A被认为是翻译启动因子,但其确切的功能尚不清楚.
- 有人假设eIF2A在压力条件下可以补偿eIF2的功能.
研究的目的:
- 研究真核转化启动因子2A (eIF2A) 在转化启动中的作用.
- 为了确定eIF2A在eIF2活动受到抑制时,在综合应激反应期间是否起作用.
主要方法:
- 在HeLa细胞中的核糖体概况.
- 路西法雷斯记者分析评估上游ORF的翻译.
- 集成应激反应的激活.
主要成果:
- 在各种实验条件下,没有观察到eIF2A在翻译启动中的可检测作用.
- 通过测试的试验无法阐明eIF2A的功能,包括在集成应激反应激活下.
结论:
- 在测试条件下,eIF2A似乎对翻译启动无关紧要.
- eIF2A的确切功能仍然难以捉摸,可能涉及在特定,未表征的条件或RNA生物学其他方面发挥作用.
相关概念视频
Initiation of Translation
34.6K
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...
34.6K
Leaky Scanning
5.2K
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
Improving Translational Accuracy
11.9K
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...
11.9K
Regulation 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
Regulated mRNA Transport
6.5K
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...
6.5K
Transcription Elongation Factors
11.2K
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...
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...
11.2K


