Zhang Luting, Lin Shengmou, Huang Kailing, Chen Allen, Li Nan, Shen Shuhan, Zheng Zhouxia, Shi Xiaoshun, Sun Jimei, Kong Jingyin, Chen Min
Department of Obstetrics and Gynecology, Department of Fetal Medicine and Prenatal Diagnosis, Key Laboratory for Major Obstetric Diseases of Guang-Dong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Obstetrics and Gynecology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Front Genet. 2023 Mar 8;14:947144. doi: 10.3389/fgene.2023.947144. eCollection 2023.
is a 118-bp segment that lies in a pair of novel non-coding RNA genes. It shows a dramatic accelerated change with an estimated 18 substitutions in the human lineage since the human-chimpanzee ancestor, compared with the expected 0.27 substitutions based on the slow rate of change in this region in other amniotes. Mutations of lead to a different HAR1 secondary structure in humans compared to that in chimpanzees. We cloned into the EF-1α promoter vector to generate transgenic mice. Morris water maze tests and step-down passive avoidance tests were conducted to observe the changes in memory and cognitive abilities of mice. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) between the experimental and control groups. Systematic bioinformatics analysis was used to confirm the pathways and functions that the DEGs were involved in. Memory and cognitive abilities of the transgenic mice were significantly improved. The results of Gene Ontology (GO) analysis showed that Neuron differentiation, Dentate gyrus development, Nervous system development, Cerebral cortex neuron differentiation, Cerebral cortex development, Cerebral cortex development and Neurogenesis are all significant GO terms related to brain development. The DEGs enriched in these terms included , , , and . All these genes play an important role in regulating the functioning of Cajal-Retzius cells (CRs). The DEGs were also enriched in glutamatergic synapses, synapses, memory, and the positive regulation of long-term synaptic potentiation. In addition, "cellular response to calcium ions" exhibited the second highest rich factor in the GO analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs showed that the neuroactive ligand-receptor interaction pathway was the most significantly enriched pathway, and DEGs also notably enriched in neuroactive ligand-receptor interaction, axon guidance, and cholinergic synapses. overexpression led to improvements in memory and cognitive abilities of the transgenic mice. The possible mechanism for this was that the long non-coding RNA (lncRNA) affected brain development by regulating the function of CRs. Moreover, may be involved in ligand-receptor interaction, axon guidance, and synapse formation, all of which are important in brain development and evolution. Furthermore, cellular response to calcium may play an important role in those processes.
是一段118个碱基对的片段，位于一对新的非编码RNA基因中。自人类与黑猩猩的共同祖先以来，人类谱系中它显示出显著加速的变化，估计有18个替换，而基于其他羊膜动物该区域缓慢的变化速率预期为0.27个替换。与黑猩猩相比，人类中 的突变导致了不同的HAR1二级结构。我们将 克隆到EF-1α启动子载体中以生成转基因小鼠。进行了莫里斯水迷宫试验和阶梯式被动回避试验，以观察小鼠记忆和认知能力的变化。进行RNA测序分析以鉴定实验组和对照组之间的差异表达基因（DEG）。使用系统的生物信息学分析来确认DEG所涉及的途径和功能。转基因小鼠的记忆和认知能力显著提高。基因本体论（GO）分析结果表明，神经元分化、齿状回发育、神经系统发育、大脑皮层神经元分化、大脑皮层发育、大脑皮层发育和神经发生都是与大脑发育相关的重要GO术语。在这些术语中富集的DEG包括 、 、 、 和 。所有这些基因在调节卡哈尔-雷茨乌斯细胞（CR）的功能中起重要作用。DEG也富集于谷氨酸能突触、突触、记忆以及长期突触增强的正调控。此外，“细胞对钙离子的反应”在GO分析中显示出第二高的富集因子。对DEG的京都基因与基因组百科全书（KEGG）分析表明，神经活性配体-受体相互作用途径是最显著富集的途径，并且DEG在神经活性配体-受体相互作用、轴突导向和胆碱能突触中也显著富集。 的过表达导致转基因小鼠记忆和认知能力的改善。其可能的机制是长链非编码RNA（lncRNA） 通过调节CR的功能影响大脑发育。此外， 可能参与配体-受体相互作用、轴突导向和突触形成，所有这些在大脑发育和进化中都很重要。此外，细胞对钙的反应可能在这些过程中起重要作用。
