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Widely spread RNA modification at neuronal synapses add functional diversity to local transcriptome

Research Project

Project/Area Number 17H03546
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology / General neuroscience
Research InstitutionKyoto University

Principal Investigator

Wang Dan Ohtan  京都大学, 高等研究院, 特定拠点准教授 (50615482)

Co-Investigator(Kenkyū-buntansha) 飯田 慶  京都大学, 医学研究科, 特定助教 (00387961)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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)
KeywordsN6-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
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (32 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (22 results) (of which Int'l Joint Research: 11 results,  Invited: 13 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] University of California at Los Angeles(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] More Dynamic, More Quantitative, Unexpectedly Intricate: Advanced Understanding on Synaptic RNA Localization in Learning and Memory2020

    • Author(s)
      Rohini R, Nobuyuki S, Wang DO*.
    • Journal Title

      Neurobiol Learn and Mem

      Volume: 168 Pages: 107149-107149

    • DOI

      10.1016/j.nlm.2019.107149

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RNA化学修飾と精神疾患 -神経シナプスからの理解2019

    • Author(s)
      助川桃枝、王丹
    • Journal Title

      医学のあゆみ

      Volume: Vol.269 No.10 Pages: 811-812

    • Related Report
      2019 Annual Research Report
  • [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.
    • Journal Title

      Nature Neuroscience

      Volume: 21 Issue: 7 Pages: 1004-1014

    • DOI

      10.1038/s41593-018-0173-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] RNAメチル化によるシナプスでの遺伝子機能分画2018

    • Author(s)
      飯田慶、王 丹*
    • Journal Title

      実験医学

      Volume: 36(19) Pages: 3227-3231

    • Related Report
      2018 Annual Research Report
  • [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
    • Journal Title

      frontiers in Molecular Biosciences

      Volume: 4 Pages: 1-12

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] miRNA Enriched in Human Neuroblast Nuclei Bind the MAZ Transcription Factor and Their Precursors Contain the MAZ Consensus Motif2017

    • Author(s)
      Belinda J. Goldie, Chantel Fitzsimmons, Judith Weidenhofer, Joshua R. Atkins, Dan O. Wang, and Murray J. Cairns
    • Journal Title

      frontiers in Molecular Neuroscience

      Volume: 10 Pages: 1-13

    • NAID

      120006936396

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Emerging Epitranscriptomics in the Synapses2019

    • Author(s)
      Wang DO et al
    • Organizer
      Indian Academy of Neuroscience
    • Related Report
      2019 Annual Research Report
  • [Presentation] Emerging Neuropitranscriptomics2019

    • Author(s)
      Wang DO et al
    • Organizer
      2019 Tzu Chi-Academia Sinica Biomedical Conference
    • Related Report
      2019 Annual Research Report
  • [Presentation] Dynamic RNA Imaging2019

    • Author(s)
      Wang DO et al
    • Organizer
      Australasian Neuroscience Society meeting
    • Related Report
      2019 Annual Research Report
  • [Presentation] RNA Epigenetics in Neurons and Synapses2019

    • Author(s)
      Wang DO
    • Organizer
      生理研研究会「記憶研究会」
    • Related Report
      2019 Annual Research Report
  • [Presentation] Synaptic Epitranscriptomics and Dynamic RNA imaging2019

    • Author(s)
      Wang DO et al
    • Organizer
      EBPS Biennial Meeting
    • Related Report
      2019 Annual Research Report
  • [Presentation] RNA modifications and translational regulation at neuronal synapses2019

    • Author(s)
      Wang DO et al
    • Organizer
      ISN-ASN
    • Related Report
      2019 Annual Research Report
  • [Presentation] Epitranscriptomics in Synapses2019

    • Author(s)
      Wang DO et al
    • Organizer
      NEURO2019, Asian Chemical Biology Initiative 2019 Yangon Meeting
    • Related Report
      2019 Annual Research Report
  • [Presentation] Emerging Neuropitranscriptomics2019

    • Author(s)
      Wang DO et al
    • Organizer
      2nd SPIRITS International Symposium
    • Related Report
      2019 Annual Research Report
  • [Presentation] Emerging Neuropitranscriptomics2018

    • Author(s)
      Wang DO et al
    • Organizer
      The 3rd National Festival and International Congress on Stem Cell and Regenerative Medicine, LSACJ Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synaptic Epitranscriptomics and Dynamic RNA Imaging2018

    • Author(s)
      Wang DO et al
    • Organizer
      EMBO symposium, Annual symposium at NIPS
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chemistry and Biology Connected for the Emergence of Consciousness2018

    • Author(s)
      Wang DO et al
    • Organizer
      24th iCeMS international symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Spatiotemporal Regulation of Gene Expression in Neurons2018

    • Author(s)
      Wang DO et al
    • Organizer
      iCeMS-iTHEMS joint workshop on Interdisciplinary Biology, Kyoto University
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synaptic m6A epitranscriptome reveals functional partition2018

    • Author(s)
      Wang DO et al
    • Organizer
      JNS Kobe
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] シナプスとmRNAの化学修飾2018

    • Author(s)
      Wang DO et al
    • Organizer
      Symposium “Open Innovation and Drug Discovery”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Emerging Epitranscriptomics and Dynamic RNA Imaging2018

    • Author(s)
      Wang DO et al
    • Organizer
      Queenstown Molecular Biology Meetings in Shanghai
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synaptic epitranscriptomics and dynamic RNA imaging in neurodevelopmentle and neuropsychiatric diseases.2017

    • Author(s)
      王丹
    • Organizer
      第40回日本分子生物学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synaptic Epitranscriptomics and Dynamic RNA Imaging in neurodevelopmentle and neuropsychiatric diseases.2017

    • Author(s)
      王丹
    • Organizer
      兵庫県立大学国際シンポジウム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synaptic epitranscriptomics and dynamic RNA imaging in neurodevelopmentle and neuropsychiatric diseases.2017

    • Author(s)
      王丹
    • Organizer
      留日中国人生命科学協会2017年度学術大会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生きた脳組織にRNA計測イメージングの開発2017

    • Author(s)
      王丹
    • Organizer
      アステラス病態代謝研究会第48回研究報告会
    • Related Report
      2017 Annual Research Report
  • [Presentation] in vivo RNA labelling reveals dynamic regulation of ribonucleic foci in living neurons2017

    • Author(s)
      王丹
    • Organizer
      日本生物物理学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Synaptic m6A Epitranscriptome Reveals Functional Partitioning of Localized Transcripts for Dynamic Tripartite Synapse Modulation2017

    • Author(s)
      王丹
    • Organizer
      第19回日本RNA学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Synaptic Epitranscriptomics and Dynamic RNA Imaging2017

    • Author(s)
      王丹
    • Organizer
      International Symposium on Imaging Frontier(ISIF 2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] RNA Detection2017

    • Author(s)
      Wang, Dan Ohtan
    • Total Pages
      489
    • Publisher
      Springer
    • ISBN
      9781493972128
    • Related Report
      2017 Annual Research Report
  • [Remarks] Synaptic N6-methyladenosine (m6A) epitranscriptome

    • URL

      https://www.rnaj.org/publications/item/637-ohtan

    • Related Report
      2018 Annual Research Report
  • [Remarks] 神経ネットワークの可塑性を支えるRNAの機能に即した化学修飾を明らかにしました

    • URL

      http://www.kyoto-u.ac.jp/ja/research/research_results/2018/180628_2.html

    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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