Tryptophan-tRNA Ligase

色氨酸 - tRNA 连接酶
  • 文章类型: Journal Article
    色氨酸-tRNA合成酶(WRS)是参与蛋白质合成的关键酶,负责向tRNA加载必需氨基酸色氨酸。最近的研究强调了其在刺激针对细菌和病毒感染的先天免疫中的新作用。然而,WRS在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染中的意义仍然难以捉摸。在这项研究中,我们的目的是调查WRS之间复杂的相互作用,炎症标志物,Toll样受体-4(TLR-4),冠状病毒病19例(COVID-19)患者的临床结局。一项病例对照调查包括127例COVID-19患者,入院时仔细分类为重度或中度,和112名健康个体作为比较组。在治疗开始前精心收集血液样本,WRS,白细胞介素-6(IL-6),和C-反应蛋白(CRP)浓度使用公认的商业ELISA试剂盒进行定量。从血液样品中分离外周血单核细胞(PBMC),提取RNA进行cDNA合成。采用半定量实时聚合酶链反应(PCR)评估TLR-4的相对表达。COVID-19患者表现出WRS水平升高,IL-6,CRP,和TLR-4表达与健康个体相比,重度组的水平明显高于中度组。值得注意的是,重症患者显示CRP大幅波动,IL-6和WRS水平随着时间的推移,在他们的温和同行中没有观察到的模式。尽管在WRS的动态变化中没有观察到明显的差异,IL-6,CRP,和TLR-4在死亡和存活患者之间的表达,出现了一种趋势,表明死亡患者的IL-6_1水平较高,而死于该疾病的重症患者的乳酸脱氢酶(LDH)水平升高。这项开创性的研究强调了COVID-19患者WRS的动态变化,为WRS之间的相关性提供有价值的见解,炎症标志物,以及该人群中疾病的严重程度。了解WRS在SARS-CoV-2感染中的作用可能会为针对先天免疫的治疗性干预措施开辟新的途径,以对抗COVID-19。
    Tryptophanyl-tRNA synthetase (WRS) is a critical enzyme involved in protein synthesis, responsible for charging tRNA with the essential amino acid tryptophan. Recent studies have highlighted its novel role in stimulating innate immunity against bacterial and viral infections. However, the significance of WRS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains elusive. In this study, we aimed to investigate the complex interplay between WRS, inflammatory markers, Toll-like receptor-4 (TLR-4), and clinical outcomes in coronavirus disease 19 (COVID-19) patients. A case-control investigation comprised 127 COVID-19 patients, carefully classified as severe or moderate upon admission, and 112 healthy individuals as a comparative group. Blood samples were meticulously collected before treatment initiation, and WRS, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were quantified using a well-established commercial ELISA kit. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples, and RNA was extracted for cDNA synthesis. Semi-quantitative real-time polymerase chain reaction (PCR) was employed to assess the relative expression of TLR-4. COVID-19 patients exhibited elevated levels of WRS, IL-6, CRP, and TLR-4 expression compared to healthy individuals, with the severe group displaying significantly higher levels than the moderate group. Notably, severe patients demonstrated substantial fluctuations in CRP, IL-6, and WRS levels over time, a pattern not observed in their moderate counterparts. Although no significant distinctions were observed in the dynamic alterations of WRS, IL-6, CRP, and TLR-4 expression between deceased and surviving patients, a trend emerged indicating higher IL-6_1 levels in deceased patients and elevated lactate dehydrogenase (LDH) levels in severe patients who succumbed to the disease. This pioneering research highlights the dynamic alterations of WRS in COVID-19 patients, providing valuable insights into the correlation between WRS, inflammatory markers, and disease severity within this population. Understanding the role of WRS in SARS-CoV-2 infection may open new avenues for therapeutic interventions targeting innate immunity to combat COVID-19.
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  • 文章类型: Journal Article
    目前数据库中可用的所有氨酰tRNA合成酶(aaRS)序列都经过了系统分析,旨在寻找基因重复,基因重组,和水平转移。提供了在这类酶中发生(或可能发生)此类现象的证据。特别是,建议来自酵母线粒体的单体PheRS是标准四聚体蛋白的α和β链的嵌合体。此外,建议GlyRS的二聚体和四聚体形式是在aaRS的两个不同亚类中双重且独立获得相同特异性的结果。编码aaRS的基因的进化史的系统发育重建被证明是非常多样化的。虽然很大一部分人口与三个Woesian域的广泛分组是一致的,一些系统发育重建并没有将神道和Eucarya作为姐妹群体,但是,更确切地说,显示革兰氏阴性细菌/真核生物聚类。此外,许多个体基因构成了阻碍任何简单进化方案的困难。因此,aaRS显然是F.Jacob的“进化的零工”的范例,但是,总的来说,不要质疑最初由Woese提出并随后由其他人改进的进化情景。
    All of the aminoacyl-tRNA synthetase (aaRS) sequences currently available in the data banks have been subjected to a systematic analysis aimed at finding gene duplications, genetic recombinations, and horizontal transfers. Evidence is provided for the occurrence (or probable occurrence) of such phenomena within this class of enzymes. In particular, it is suggested that the monomeric PheRS from the yeast mitochondrion is a chimera of the alpha and beta chains of the standard tetrameric protein. In addition, it is proposed that the dimeric and tetrameric forms of GlyRS are the result of a double and independent acquisition of the same specificity within two different subclasses of aaRS. The phylogenetic reconstructions of the evolutionary histories of the genes encoding aaRS are shown to be extremely diverse. While large segments of the population are consistent with the broad grouping into the three Woesian domains, some phylogenetic reconstructions do not place the Archae and the Eucarya as sister groups but, rather, show a gram-negative bacteria/eukaryote clustering. In addition, many individual genes pose difficulties that preclude any simple evolutionary scheme. Thus, aaRS\'s are clearly a paradigm of F. Jacob\'s \"odd jobs of evolution\" but, on the whole, do not call into question the evolutionary scenario originally proposed by Woese and subsequently refined by others.
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