Mouse Nsmce1 gene is the homolog of non-structural maintenance of chromosomes element 1 (NSE1) that is mainly involved in maintenance of genome integrity, DNA damage response, and DNA repair. Defective DNA repair may cause neurological disorders such as Alzheimer’s disease (AD). So far, there is no direct evidence for the correlation between Nsmce1 and AD. In order to explore the function of Nsmce1 in the regulation of nervous system, we have overexpressed or knocked down Nsmce1 in the mouse hippocampal neuronal cells (MHNCs) HT-22 and detected its regulation of AD marker genes as well as cell proliferation. The results showed that the expression of App, Bace2, and Mapt could be inhibited by Nsmce1 overexpression and activated by the knockdown of Nsmce1. Moreover, the HT-22 cell proliferation ability could be promoted by Nsmce1 overexpression and inhibited by knockdown of Nsmce1. Furthermore, we performed a transcriptomics study by RNA sequencing (RNA-seq) to evaluate and quantify the gene expression profiles in response to the overexpression of Nsmce1 in HT-22 cells. As a result, 224 significantly dysregulated genes including 83 upregulated and 141 downregulated genes were identified by the comparison of Nsmce1 /+ to WT cells, which were significantly enriched in several Gene Ontology (GO) terms and pathways. In addition, the complexity of the alternative splicing (AS) landscape was increased by Nsmce1 overexpression in HT-22 cells. Thousands of AS events were identified to be mainly involved in the pathway of ubiquitin-mediated proteolysis (UMP) as well as 3 neurodegenerative diseases including AD. The protein-protein interaction network was reconstructed to show top 10 essential genes regulated by Nsmce1. Our sequencing data is available in the Gene Expression Omnibus (GEO) database with accession number as GSE113436. These results may provide some evidence of molecular and cellular functions of Nsmce1 in MHNCs.

中文翻译：

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RNA测序对小鼠海马神经元细胞中Nsmce1过表达的转录组学分析。

小鼠Nsmce1基因是染色体元素1（NSE1）的非结构维护的同源物，其主要参与基因组完整性的维护，DNA损伤反应和DNA修复。DNA修复缺陷可能会导致神经系统疾病，例如阿尔茨海默氏病（AD）。到目前为止，尚无直接证据表明Nsmce1与AD之间存在相关性。为了探索Nsmce1在神经系统调节中的功能，我们在小鼠海马神经元细胞（MHNCs）HT-22中过表达或敲低了Nsmce1，并检测了其对AD标记基因的调节以及细胞增殖。结果表明App，Bace2和Mapt的表达可能被Nsmce1过表达抑制并被Nsmce1的敲低激活。此外，HT-22细胞增殖的能力可通过促进Nsmce1过表达和通过敲除抑制Nsmce1。此外，我们通过RNA测序（RNA-seq）进行了转录组学研究，以评估和量化响应HT-22细胞中Nsmce1过表达的基因表达谱。结果，通过比较Nsmce1，鉴定出224个严重失调的基因，包括83个上调的基因和141个下调的基因。/ +转移至WT细胞，这些细胞在几种基因本体论（GO）术语和途径中显着丰富。此外，HT-22细胞中Nsmce1过表达增加了选择性剪接（AS）格局的复杂性。确定了成千上万的AS事件主要与泛素介导的蛋白水解（UMP）以及包括AD在内的3种神经退行性疾病有关。重建蛋白质-蛋白质相互作用网络以显示受Nsmce1调控的前10个必需基因。我们的测序数据可在基因表达综合（GEO）数据库中获得，登录号为GSE113436。这些结果可能为MHNCs中Nsmce1的分子和细胞功能提供一些证据。