| 研究実績の概要 |
The goal of this project is to understand the function of N6-methyladenosine (m6A), a highly prevalent mRNA modification in the brain. m6A has been reported to increases along aging and regulates expression level of many proteins important for neuronal signaling, including dopamine receptors. Variations in the m6A modification enzymes not only predispose to obesity in humans, but also are associated with aging-dependent reduced brain volume, loss of memory, and risk of alcohol dependence. We hypothesized that m6A modulates spatiotemporal regulation of neuronal gene expression at synapse, which in turn, regulate cellular response of neurons to learning-related stimuli to store information of past events. This cellular mechanism may play critically important roles in aging-, nutrition-, alcohol-dependent memory dynamism. Within two years, we have successfully devised a sequencing methods using low-input amount of RNA materials and generated a list of genes that are localized to neuronal synapses by performing immuno-capture of m6A followed by deep sequencing. The data are directing to a synaptic epitranscriptomics scheme that may regulate local synaptic function by regulating local RNA dynamics. Such dynamic regulation is highly likely to play a critical role in rapid response to various stimuli that neurons receive such as learning-related activities. Currently the results are being analyzed for publication in high-impact journals.
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