Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Sci Rep. 2017 Mar 16;7:44500. doi: 10.1038/srep44500.
Amyotrophic lateral sclerosis (ALS) is a multifactorial lethal motor neuron disease with no known treatment. Although the basic mechanism of its degenerative pathogenesis remains poorly understood, a subcellular spatial alteration in RNA metabolism is thought to play a key role. The nature of these RNAs remains elusive, and a comprehensive characterization of the axonal RNAs involved in maintaining neuronal health has yet to be described. Here, using cultured spinal cord (SC) neurons grown using a compartmented platform followed by next-generation sequencing (NGS) technology, we find that RNA expression differs between the somatic and axonal compartments of the neuron, for both mRNA and microRNA (miRNA). Further, the introduction of SOD1 and TDP43, established ALS-related mutations, changed the subcellular expression and localization of RNAs within the neurons, showing a spatial specificity to either the soma or the axon. Altogether, we provide here the first combined inclusive profile of mRNA and miRNA expression in two ALS models at the subcellular level. These data provide an important resource for studies on the roles of local protein synthesis and axon degeneration in ALS and can serve as a possible target pool for ALS treatment.
肌萎缩侧索硬化症（ALS）是一种多因素致死性运动神经元疾病，目前尚无已知的治疗方法。尽管其退行性发病机制的基本机制仍不清楚，但人们认为细胞内 RNA 代谢的亚细胞空间改变起着关键作用。这些 RNA 的性质仍然难以捉摸，对于参与维持神经元健康的轴突 RNA 的全面描述尚未描述。在这里，我们使用使用分隔平台培养的脊髓（SC）神经元，然后使用下一代测序（NGS）技术，发现神经元的体细胞和轴突区之间的 RNA 表达存在差异，mRNA 和 microRNA（miRNA）都是如此。此外，引入 SOD1 和 TDP43，这两种已建立的 ALS 相关突变，改变了神经元内 RNA 的亚细胞表达和定位，显示出对体或轴突的空间特异性。总的来说，我们在这里提供了两个 ALS 模型在亚细胞水平上的 mRNA 和 miRNA 表达的首次综合全面分析。这些数据为研究局部蛋白质合成和轴突退化在 ALS 中的作用提供了重要资源，并可作为 ALS 治疗的可能靶标池。
