Han Min, Liu Zhen, Xu Yingying, Liu Xiangtian, Wang Dewei, Li Fan, Wang Yun, Bi Jianzhong
Department of General Medicine, The Second Hospital of Shandong University, Jinan, China.
Department of Neurology Medicine, Second Hospital of Shandong University, Jinan, China.
Front Neurosci. 2020 Feb 28;14:98. doi: 10.3389/fnins.2020.00098. eCollection 2020.
Alzheimer's disease (AD), the most common form of dementia, is highly prevalent in older adults. The main clinical feature is the progressive decline of memory function, which eventually leads to the decline of cognitive function. At present, the pathogenesis of AD is unclear. In the disease process, synaptic changes are the key. Recent studies have shown that the dysregulation of RNA methylation is related to many biological processes, including neurodevelopment and neurodegenerative diseases. N6-methyladenosine (m6A) is the most abundant modification in eukaryotic RNA. In this study, RNA m6A methylation was quantified in APP/PS1 transgenic mice, which is an AD mouse model, and C57BL/6 control mice, and data showed that m6A methylation was elevated in the cortex and the hippocampus of APP/PS1 transgenic mice. Next, the alterations of m6A RNA methylation in AD and in C57BL/6 mice were investigated using high-throughput sequencing. Genome-wide maps of m6A mRNA showed that the degrees of m6A methylation were higher in many genes and lower in others in AD mice. Interestingly, the expression of the m6A methyltransferase METTL3 was elevated and that of the m6A demethylase FTO was decreased in AD mice. The data were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and pathways that might be related to synaptic or neuron development and growth were constructed. The related pathways and genes predicted the potential roles of the differentially expressed m6A methylation RNA in AD. Collectively, our findings demonstrate that the m6A methylation of RNA promotes the development of AD.
阿尔茨海默病（AD）是最常见的痴呆形式，在老年人中高度流行。其主要临床特征是记忆功能进行性衰退，最终导致认知功能下降。目前，AD的发病机制尚不清楚。在疾病过程中，突触变化是关键。最近的研究表明，RNA甲基化失调与许多生物学过程有关，包括神经发育和神经退行性疾病。N6-甲基腺苷（m6A）是真核RNA中最丰富的修饰。在本研究中，对AD小鼠模型APP/PS1转基因小鼠和C57BL/6对照小鼠的RNA m6A甲基化进行了定量，数据显示APP/PS1转基因小鼠的皮质和海马中m6A甲基化升高。接下来，使用高通量测序研究了AD小鼠和C57BL/6小鼠中m6A RNA甲基化的变化。全基因组m6A mRNA图谱显示，AD小鼠中许多基因的m6A甲基化程度较高，而其他基因的m6A甲基化程度较低。有趣的是，AD小鼠中m6A甲基转移酶METTL3的表达升高，而m6A去甲基化酶FTO的表达降低。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析对数据进行了分析，并构建了可能与突触或神经元发育和生长相关的通路。相关通路和基因预测了差异表达的m6A甲基化RNA在AD中的潜在作用。总的来说，我们的研究结果表明RNA的m6A甲基化促进了AD的发展。
