School of Life Sciences, Central University of Gujarat, Gandhinagar, India.
Dana Farber Cancer Institute, Boston, Massachusetts, USA.
FASEB J. 2023 Nov;37(11):e23219. doi: 10.1096/fj.202202024RR.
Aminoacyl-tRNA synthetases (AaRSs) are valuable "housekeeping" enzymes that ensure the accurate transmission of genetic information in living cells, where they aminoacylated tRNA molecules with their cognate amino acid and provide substrates for protein biosynthesis. In addition to their translational or canonical function, they contribute to nontranslational/moonlighting functions, which are mediated by the presence of other domains on the proteins. This was supported by several reports which claim that AaRS has a significant role in gene transcription, apoptosis, translation, and RNA splicing regulation. Noncanonical/ nontranslational functions of AaRSs also include their roles in regulating angiogenesis, inflammation, cancer, and other major physio-pathological processes. Multiple AaRSs are also associated with a broad range of physiological and pathological processes; a few even serve as cytokines. Therefore, the multifunctional nature of AaRSs suggests their potential as viable therapeutic targets as well. Here, our discussion will encompass a range of noncanonical functions attributed to Aminoacyl-tRNA Synthetases (AaRSs), highlighting their links with a diverse array of human diseases.
氨酰-tRNA 合成酶（Aminoacyl-tRNA Synthetases，AaRSs）是一种有价值的“管家”酶，可确保活细胞中遗传信息的准确传递，它们将 tRNA 分子与相应的氨基酸氨酰化，并为蛋白质生物合成提供底物。除了其翻译或典型功能外，它们还具有非翻译/兼职功能，这些功能由蛋白质上其他结构域的存在介导。这得到了几项报告的支持，这些报告声称 AaRS 在基因转录、细胞凋亡、翻译和 RNA 剪接调节中具有重要作用。AaRS 的非典型/非翻译功能还包括在调节血管生成、炎症、癌症和其他主要生理病理过程中的作用。多种 AaRS 也与广泛的生理和病理过程有关；少数甚至作为细胞因子发挥作用。因此，AaRS 的多功能性质表明它们具有作为可行的治疗靶点的潜力。在这里，我们的讨论将涵盖归因于氨酰-tRNA 合成酶（AaRSs）的一系列非典型功能，强调它们与多种人类疾病的联系。
