单核细胞启动因子6是翻译,生长和转化速度的限制
Valentina Gandin1, Annarita Miluzio, Anna Maria Barbieri
1Molecular Histology and Cell Growth Laboratory, San Raffaele Science Institute, Via Olgettina 58, 20132 Milan, Italy.
Nature
|September 12, 2008
概括
哺乳动物真核细胞启动因子6 (eIF6) 对于细胞生长至关重要,它将细胞外信号与翻译启动联系起来. 降低eIF6水平会损害细胞增殖并导致胚胎死亡,突出其在细胞周期进展中的关键作用.
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:
- 细胞生长和增殖取决于协调的核糖体生物发生和翻译.
- 细胞启动因子 (eIFs) 在限制速率的启动阶段调节翻译.
- 现有的eIF通过40S核糖体子单元将细胞外刺激与翻译联系起来,但不是60S子单元.
研究的目的:
- 研究哺乳动物真核细胞启动因子6 (eIF6) 在翻译启动中的作用及其与细胞外刺激的联系.
- 确定eIF6在哺乳动物发育和细胞周期进展中的体内功能.
主要方法:
- 产生和分析eIF6无和异合的小鼠及其胚胎纤维细胞.
- 评估核糖体生物发生,翻译启动和细胞周期进展 (G1/S阶段).
- 评估eIF6的胰岛素刺激转化和瘤基因诱导的转化.
主要成果:
- eIF6无胚胎在植入前阶段是致命的.
- 异卵性小鼠 (eIF6(+/-)) 显示eIF6水平降低,肝脏和脂肪组织质量减少,G1/S细胞周期进展受损.
- eIF6(+/-) 细胞表现出正常的核糖体生物发生,但在翻译启动中存在缺陷,胰岛素刺激的翻译受损,并且对瘤转化有抵抗性.
结论:
- 哺乳动物eIF6对于高效的翻译启动至关重要,它将细胞外信号与60S核糖体子单元的活动联系起来.
- eIF6在胚胎发育,细胞增殖和细胞周期控制中发挥着至关重要的作用.
- eIF6是一种新型的翻译启动调节剂,对了解细胞生长和癌症发展有意义.
相关概念视频
02:35Transcription Elongation Factors
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 into a...
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 into a...
02:07Improving Translational Accuracy
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...
02:33Initiation of Translation
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...
02:35Transcription Elongation Factors
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 into a...
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 into a...
02:33Initiation of Translation
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...
01:29Translation in Prokaryotes
Prokaryote translation is a complex, highly coordinated process that converts genetic information from mRNA into functional proteins. It involves three stages: initiation, elongation, and termination, each facilitated by specific molecular components.Initiation of TranslationThe process begins with the assembly of the ribosomal subunits and initiation factors on the mRNA. In bacteria, the 30S ribosomal subunit recognizes the Shine-Dalgarno sequence in the mRNA, a conserved region upstream of...