Widely spread RNA modification at neuronal synapses add functional diversity to local transcriptome
| Project/Area Number |
17H03546
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurophysiology / General neuroscience
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| Research Institution | Kyoto University |
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Principal Investigator |
Wang Dan Ohtan 京都大学, 高等研究院, 特定拠点准教授 (50615482)
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| Co-Investigator(Kenkyū-buntansha) |
飯田 慶 京都大学, 医学研究科, 特定助教 (00387961)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | N6-adenosine methvlation / 機能分画 / シナブトソーム / 翻訳制御 / 精神疾患 / 発達障害 / N6-adenosine methylation / シナプトソーム / 地方分権型遺伝子制御 / 局所翻訳 / 成長円錐 / 微小管 / epitranscriptomics / local translation / dynamics / epitranscriptome / N6-adenosine / RNA lcoalization / synaptic plasticity / mRNA / chemical modification / methylation / synapse / localization |
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| Outline of Final Research Achievements |
The brain is an intricate and complex organ that underlies our cognition and behavior. To understand how our genetic information is transformed into brain function, we have focused on RNA chemical modifications within synapses that contribute to circuitry for learning and conscious perception. Now we have revealed an unexplored regulatory mechanism of dynamic gene expression for the synthesis and modulation of tripartite synapses, and for brain pathways implicated in neurodevelopmental and neuropsychiatric diseases. This work indicates that simple chemical modifications, such as addition of a methyl group (-CH3) to the RNA molecules, can make critical contributions to building neuronal connections in the brain and thus the emergence of individual consciousness. Future directions will be focused on how these local synaptic changes in the epitranscriptome may influence learning and conscious perception.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、m6Aをはじめ次々とmRNAの新たな修飾が網羅的に同定されるようになったが、各細胞の運命決定における意義の解明は着手されたばかりである。申請者は既存のエピジェネティクスモデルでは解決できない「迅速さ」と「柔軟性」をもつ神経遺伝子情報発現新制御相を明らかにする。応用としては、遺伝性のない神経変性疾患において、mRNA修飾制御が新たな研究対象として展開されることが期待できる。本研究成果を皮切りに、様々な化学修飾がmRNAメタ情報として、神経細胞のみならず広範な生命現象の制御因子として、より一般的な概念として波及していく効果も期待される。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Synaptic m6A Epitranscriptome Reveals Functional Partitioning of Localized Transcripts for Dynamic Tripartite Synapse Modulation.2018
Author(s)
Merkurjev, D., Hong, W. T., Iida, K., Oomoto, I., Goldie, B. J., Yamaguti, H., Ohara, T. Kawaguchi, S. Y., Hirano, T., Martin, K. C., Pellegrini, M. & Wang, D. O.
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Journal Title
Nature Neuroscience
Volume: 21
Issue: 7
Pages: 1004-1014
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Transport Granules Bound with Nuclear Cap Binding Protein and Exon Junction Complex Are Associated with Microtubules and Spatially Separated from eIF4E Granules and P Bodies in Human Neuronal Processes2017
Author(s)
Wang DO, Ninomiya K, Mori C, Koyama A, Haan M, Kitabatake M, Hagiwara M, Chida K, Takahashi SI, Ohno M, Kataoka N
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Journal Title
frontiers in Molecular Biosciences
Volume: 4
Pages: 1-12
Related Report
Peer Reviewed / Open Access
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