Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Enzymes. 2020;48:207-242. doi: 10.1016/bs.enz.2020.04.001. Epub 2020 Jun 12.
Aminoacyl-tRNA synthetases catalyze the aminoacylation of their cognate tRNAs. Here we review the accumulated knowledge of non-canonical functions of human cytoplasmic aminoacyl-tRNA synthetases, especially tyrosyl- (TyrRS) and tryptophanyl-tRNA synthetase (TrpRS). Human TyrRS and TrpRS have an extra domain. Two distinct cytokines, i.e., the core catalytic "mini TyrRS" and the extra C-domain, are generated from human TyrRS by proteolytic cleavage. Moreover, the core catalytic domains of human TyrRS and TrpRS function as angiogenic and angiostatic factors, respectively, whereas the full-length forms are inactive for this function. It is also known that many synthetases change their localization in response to a specific signal and subsequently exhibit alternative functions. Furthermore, some synthetases function as sensors for amino acids by changing their protein interactions in an amino acid-dependent manner. Further studies will be necessary to elucidate regulatory mechanisms of non-canonical functions of aminoacyl-tRNA synthetases in particular, by analyzing the effect of their post-translational modifications.
氨酰-tRNA 合成酶催化其对应的 tRNA 的氨酰化。在这里，我们回顾了人类细胞质氨酰-tRNA 合成酶（尤其是酪氨酸-tRNA 合成酶（TyrRS）和色氨酰-tRNA 合成酶（TrpRS））的非典型功能的积累知识。人类 TyrRS 和 TrpRS 具有额外的结构域。两种不同的细胞因子，即核心催化“迷你 TyrRS”和额外的 C 结构域，通过蛋白水解切割从人类 TyrRS 中产生。此外，人类 TyrRS 和 TrpRS 的核心催化结构域分别作为血管生成和血管抑制因子发挥作用，而全长形式对此功能无活性。此外，许多合成酶会响应特定信号改变其定位，随后表现出替代功能。此外，一些合成酶通过改变其蛋白相互作用的氨基酸依赖性方式作为氨基酸传感器发挥作用。进一步的研究将需要通过分析其翻译后修饰的影响来阐明氨酰-tRNA 合成酶的非典型功能的调节机制。
