对于eIF4GI驱动的结构化mRNAs的封顶独立翻译的真核细胞启动因子要求的机制差异
Baishakhi Saha1, Solomon A Haizel2, Dixie J Goss3
1Department of Chemistry, Hunter College, City University of New York, New York, New York, USA.
The Journal of biological chemistry
|October 9, 2024
概括
细胞压力降低了蛋白质翻译的调节,但使用结构化的5'UTRs的独立路径至关重要. 这项研究揭示了FGF-9和HIF-1αmRNA翻译启动的独特机制,涉及特定的启动因子.
科学领域:
- 分子生物学分子生物学
- 基因表达规范 基因表达规范
- 蛋白质合成 蛋白质合成
背景情况:
- 在细胞压力期间,蛋白质翻译在全球范围内减少.
- 顶部独立的翻译启动对于应激反应蛋白质合成至关重要.
- 在mRNA中结构化的5'UTRs通过增强剂或IRES元素促进顶部独立的翻译.
研究的目的:
- 为了研究翻译启动因子 (eIF4E,eIF4A,eIF4GI) 招募到结构化的5'UTR.
- 阐明这些因素在FGF-9和HIF-1αmRNA非正规翻译启动中的作用.
- 了解基于5'UTR结构的上限独立翻译的差异调节.
主要方法:
- 平衡结合试验用于量化因子-RNA相互作用.
- 循环二元化 (CD) 研究以检测形状变化.
- 在体外翻译测试以评估翻译效率.
主要成果:
- eIF4A和eIF4E增强了eIF4GI与HIF-1αmRNA结构化的5'UTR的结合,诱导了形状变化.
- 这些因素没有影响eIF4GI与FGF-9mRNA的结构化5'UTR的结合.
- 与结构化5'UTRs的结合减轻了与非结构化RNA所见的特定因子状态 (例如,ATP结合的eIF4A) 的要求.
结论:
- 对于FGF-9和HIF-1αmRNAs,提出了两个截然不同的上限独立的翻译机制.
- 细胞应激反应利用针对不同5'UTR结构的特定启动因子相互作用.
- 这突显了翻译机制在压力下调节基因表达的适应性.
相关概念视频
02:33Initiation of Translation
31.7K
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...
31.7K
02:07Improving Translational Accuracy
9.4K
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...
9.4K
02:28Leaky 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
02:53Ribosomal RNA Synthesis
13.1K
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
13.1K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.0K
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...
7.0K
02:35Transcription Elongation Factors
10.8K
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...
10.8K