Predicting the pathogenicity of aminoacyl-tRNA synthetase mutations.
Predicting the pathogenicity of aminoacyl-tRNA synthetase mutations.
复制标题
预测氨基酰基-TRNA合成酶突变的致病性。
DOI：
10.1016/j.ymeth.2016.11.013
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发表时间：
2017-01-15
期刊：
影响因子：
--
通讯作者：
Antonellis A
中科院分区：
文献类型：
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作者：
Oprescu SN;Griffin LB;Beg AA;Antonellis A
氨酰基-tRNA 合成酶 (ARS) 是一种普遍表达的必需酶，负责为 tRNA 添加同源氨基酸，这是蛋白质合成的第一步。所有细胞的细胞质和线粒体中的蛋白质翻译都需要 ARS。令人惊讶的是，37 个核编码的人类 ARS 基因中有 28 个的突变与多种隐性和显性组织特异性疾病有关。目前的数据表明，酶功能受损是 ARS 突变致病性的有力预测因素。然而，需要区分致病性和非致病性 ARS 变异的实验模型系统来暗示疾病中新发现的 ARS 突变。在这里，我们概述了帮助预测 ARS 变异致病性的策略，并敦促在将 ARS 突变与人类疾病表型联系起来之前谨慎评估遗传和功能数据。
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes responsible for charging tRNA with cognate amino acids—the first step in protein synthesis. ARSs are required for protein translation in the cytoplasm and mitochondria of all cells. Surprisingly, mutations in 28 of the 37 nuclear-encoded human ARS genes have been linked to a variety of recessive and dominant tissue-specific disorders. Current data sustains that impaired enzyme function is a robust predictor of the pathogenicity of ARS mutations. However, experimental model systems that distinguish between pathogenic and non-pathogenic ARS variants are required for implicating newly identified ARS mutations in disease. Here, we outline strategies to assist in predicting the pathogenicity of ARS variants and urge cautious evaluation of genetic and functional data prior to linking an ARS mutation to a human disease phenotype.