体外和细胞内检测氨基酰化和氨基酰-tRNA 编辑的策略

IF 2.3 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Rylan R. Watkins, Arundhati Kavoor, Prof. Karin Musier-Forsyth
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引用次数: 0

摘要

氨基酰-tRNA 合成酶(aaRS)通过确保形成正确的氨基酰-tRNA 对来维持翻译的保真度。人类 aaRSs 的许多点突变都与疾病表型有关。对人类病原体中编码独特结构域的 aaRS 的结构研究支持将这些酶作为潜在的候选疗法。研究表明,细胞中 tRNA 池的特性在不同细胞类型和应激条件下会发生变化。虽然传统的放射性氨基酰化分析可以确定致病突变对 aaRS 功能的影响,但这些检测方法不适合药物发现活动,也没有考虑到细胞内 tRNA 池的可变性。在此,我们回顾了表征体外和细胞内 aaRS 活性的现代技术。基于细胞的方法分析氨基酰-tRNA 池,观察 aaRS 活性和保真度的趋势。总之,这些方法可以对 aaRS 抑制剂进行高通量药物筛选,并在各种条件和疾病状态下对动态 tRNA 群体进行系统级分析。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Strategies for Detecting Aminoacylation and Aminoacyl-tRNA Editing in vitro and in Cells

Strategies for Detecting Aminoacylation and Aminoacyl-tRNA Editing in vitro and in Cells

Aminoacyl-tRNA synthetases (aaRSs) maintain translational fidelity by ensuring the formation of correct aminoacyl-tRNA pairs. Numerous point mutations in human aaRSs have been linked to disease phenotypes. Structural studies of aaRSs from human pathogens encoding unique domains support these enzymes as potential candidates for therapeutics. Studies have shown that the identity of tRNA pools in cells changes between different cell types and under stress conditions. While traditional radioactive aminoacylation analyses can determine the effect of disease-causing mutations on aaRS function, these assays are not amenable to drug discovery campaigns and do not take into account the variability of the intracellular tRNA pools. Here, we review modern techniques to characterize aaRS activity in vitro and in cells. The cell-based approaches analyse the aminoacyl-tRNA pool to observe trends in aaRS activity and fidelity. Taken together, these approaches allow high-throughput drug screening of aaRS inhibitors and systems-level analyses of the dynamic tRNA population under a variety of conditions and disease states.

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来源期刊
Israel Journal of Chemistry
Israel Journal of Chemistry 化学-化学综合
CiteScore
6.20
自引率
0.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The fledgling State of Israel began to publish its scientific activity in 1951 under the general heading of Bulletin of the Research Council of Israel, which quickly split into sections to accommodate various fields in the growing academic community. In 1963, the Bulletin ceased publication and independent journals were born, with Section A becoming the new Israel Journal of Chemistry. The Israel Journal of Chemistry is the official journal of the Israel Chemical Society. Effective from Volume 50 (2010) it is published by Wiley-VCH. The Israel Journal of Chemistry is an international and peer-reviewed publication forum for Special Issues on timely research topics in all fields of chemistry: from biochemistry through organic and inorganic chemistry to polymer, physical and theoretical chemistry, including all interdisciplinary topics. Each topical issue is edited by one or several Guest Editors and primarily contains invited Review articles. Communications and Full Papers may be published occasionally, if they fit with the quality standards of the journal. The publication language is English and the journal is published twelve times a year.
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