Abstract
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.
Highlights
The incidence of Alzheimer’s disease (AD) in many countries around the world is very high due to a lack of effective treatments (Bateman et al, 2012)
methyltransferase-like protein 3 (METTL3) is the at the center of catalytic methyl reactions, and FTO, which is abundant in rat brains, is related to neurotransmitter delivery and nervous system development (Li et al, 2017, 2018). m6A RNA methylation, regarded as a new frontier in neuroscience, could provide us with a better understanding of neural development and neurological diseases from a novel perspective
APP/PS1 double transgenic mouse models are often used as a simulation of AD animal models
Summary
The incidence of Alzheimer’s disease (AD) in many countries around the world is very high due to a lack of effective treatments (Bateman et al, 2012). Some studies have shown that m6A is related to the development of the nervous system and to neural degenerative diseases (Meyer et al, 2012; Widagdo et al, 2016; Li et al, 2018), but the role of the regulatory mechanism is still unknown. METTL3 is the at the center of catalytic methyl reactions, and FTO, which is abundant in rat brains, is related to neurotransmitter delivery and nervous system development (Li et al, 2017, 2018). M6A RNA methylation, regarded as a new frontier in neuroscience, could provide us with a better understanding of neural development and neurological diseases from a novel perspective. M6A RNA methylation in the brains of AD and of control mice were investigated by high-throughput sequencing and the differences were compared. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the function of differentially expressed RNAs
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