Institute of Protein Research, Pushchino, Moscow Region, 142290, Russia.
Biochemistry (Mosc). 2021 Jan;86(Suppl 1):S12-S23. doi: 10.1134/S0006297921140029.
Aminoacyl-RNA synthetases (aaRSs) are among the key enzymes of protein biosynthesis. They are responsible for conducting the first step in the protein biosynthesis, namely attaching amino acids to the corresponding tRNA molecules both in cytoplasm and mitochondria. More and more research demonstrates that mutations in the genes encoding aaRSs lead to the development of various neurodegenerative diseases, such as incurable Charcot-Marie-Tooth disease (CMT) and distal spinal muscular atrophy. Some mutations result in the loss of tRNA aminoacylation activity, while other mutants retain their classical enzyme activity. In the latter case, disease manifestations are associated with additional neuron-specific functions of aaRSs. At present, seven aaRSs (GlyRS, TyrRS, AlaRS, HisRS, TrpRS, MetRS, and LysRS) are known to be involved in the CMT etiology with glycyl-tRNA synthetase (GlyRS) being the most studied of them.
氨酰-tRNA 合成酶（aaRSs）是蛋白质生物合成的关键酶之一。它们负责在细胞质和线粒体中进行蛋白质生物合成的第一步，即将氨基酸连接到相应的 tRNA 分子上。越来越多的研究表明，编码 aaRSs 的基因突变会导致各种神经退行性疾病的发生，如无法治愈的夏科-马里-图思病（CMT）和远端脊髓性肌萎缩症。一些突变导致 tRNA 氨酰化活性丧失，而其他突变体保留其经典的酶活性。在后一种情况下，疾病表现与 aaRSs 的其他神经元特异性功能有关。目前，已知有七种 aaRSs（GlyRS、TyrRS、AlaRS、HisRS、TrpRS、MetRS 和 LysRS）与 CMT 的病因有关，其中 GlyRS 是研究最多的一种。
