Disease Target Structure Research Center, KRIBB, Daejeon, South Korea; KRIBB School, University of Science and Technology, Daejeon, South Korea; Dementia DTC R&D Convergence Program, KIST, Seoul, South Korea.
Disease Target Structure Research Center, KRIBB, Daejeon, South Korea; KRIBB School, University of Science and Technology, Daejeon, South Korea; Dementia DTC R&D Convergence Program, KIST, Seoul, South Korea.
Biochem Biophys Res Commun. 2022 Jan 8;587:92-98. doi: 10.1016/j.bbrc.2021.11.098. Epub 2021 Nov 29.
Aminoacyl tRNA synthetases (ARSs) are a group of proteins, acting as transporters to transfer and attach the appropriate amino acids onto their cognate tRNAs for translation. So far, 18 out of 20 cytoplasmic ARSs are reported to be connected to different neuropathy disorders with multi-organ defects that are often accompanied with developmental delays. Thus, it is important to understand functions and impacts of ARSs at the whole organism level. Here, we systematically analyzed the spatiotemporal expression of 14 ars and 2 aimp genes during development in zebrafish that have not be previously reported. Not only in the brain, their dynamic expression patterns in several tissues such as in the muscles, liver and intestine suggest diverse roles in a wide range of development processes in addition to neuronal function, which is consistent with potential involvement in multiple syndrome diseases associated with ARS mutations. In particular, hinted by its robust expression pattern in the brain, we confirmed that aimp1 is required for the formation of cerebrovasculature by a loss-of-function approach. Overall, our systematic profiling data provides a useful basis for studying roles of ARSs during development and understanding their potential functions in the etiology of related diseases.
氨酰-tRNA 合成酶(ARSs)是一组蛋白质,作为转运体将合适的氨基酸转移并连接到其对应的 tRNA 上,以进行翻译。到目前为止,据报道,20 种细胞质 ARSs 中的 18 种与多种神经病变疾病有关,这些疾病通常伴有多器官缺陷和发育迟缓。因此,了解 ARSs 在整个生物体水平上的功能和影响非常重要。在这里,我们系统地分析了在斑马鱼发育过程中以前未报道过的 14 种 ars 和 2 种 aimp 基因的时空表达。不仅在大脑中,它们在肌肉、肝脏和肠道等几种组织中的动态表达模式表明,除了神经元功能外,它们在广泛的发育过程中具有多样化的作用,这与与 ARS 突变相关的多种综合征疾病的潜在相关性一致。特别是,鉴于其在大脑中的强表达模式,我们通过功能丧失方法证实 aimp1 对于脑血管形成是必需的。总的来说,我们的系统分析数据为研究 ARSs 在发育过程中的作用以及理解它们在相关疾病发病机制中的潜在功能提供了有用的基础。