天生的免疫和化学触发的氧化应激改变了翻译忠实性
Nir Netzer1, Jeffrey M Goodenbour, Alexandre David
1Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Nature
|November 27, 2009
概括
转移RNAs (tRNAs) 的 metionin 错解发生在哺乳动物细胞中,在压力下增加. 这一过程可能会通过适应性增强对反应性氧物种 (ROS) 的蛋白质保护.
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:
- 转化忠实性对于蛋白质合成和细胞功能至关重要,它依赖于精确的转移RNA (tRNA) 氨基化.
- 虽然纯化的氨基酸-tRNA合成酶显示出高保真性,但体内准确性仍然不确定.
- 已知氨酸 (Met) 残留物可以保护蛋白质免受氧化损伤.
研究的目的:
- 为了研究哺乳动物细胞中tRNA氨基化过程的准确性.
- 为了确定是否发生甲氨酸失调,以及在什么条件下.
- 探索Met-misacylation在抗氧化应激的细胞防御中的潜在适应作用.
主要方法:
- 在哺乳动物细胞中的Met-misacylation的量化.
- 细胞暴露于各种压力因素,包括病毒,类似收费的受体连接体和氧化应激剂.
- 抑制细胞氧化酶以识别错位化触发因素.
- 在六种不同的氨基酸中测试错化.
主要成果:
- 在哺乳动物细胞中,大约1%的Met残留物被错基化为非甲基-tRNA.
- 在病毒,TLR连接体或氧化应激条件下,甲基-脱氧化增加了多达十倍.
- 甲基分离是由活性氧物种 (ROS) 触发的,并且在测试的氨基酸中仅与甲基发生.
- 在蛋白质翻译中使用met-misacylatedtRNAs.
结论:
- 甲氨酸失调是哺乳动物细胞中条件和压力诱导的现象.
- 反应性氧物种 (ROS) 被认为是Met-misacylation的触发因素.
- 甲基分离可能起到适应作用,增加 metionin 纳入蛋白质,以增强细胞对氧化应激的保护.
- 这些发现表明mRNA解码的条件方面,并强调考虑替代遗传代码解释的重要性.
相关概念视频
01:31Translation
162.6K
Lesson: Translation
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...
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...
162.6K
01:53RNA Stability
36.5K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
36.5K
02:07Improving Translational Accuracy
15.7K
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...
15.7K
01:31Regulation of the Unfolded Protein Response
3.2K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
01:31Translation
23.3K
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...
23.3K
01:29Translational Regulation
875
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
875