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mRNA chemical modification in activity-dependent establishment of neural circuits

Research Project

Project/Area Number 21H02580
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Wang Dan Ohtan  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (50615482)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2022: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2021: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords軸索 / RNA化学修飾 / シナプス / epidecodeR / reader protein / YTHDF1 / スパイン / ythdf3 / environement / depression / RNA modification / RNA adduction / RNA methylation / APC / prefrontal cortex / sex / 微小管 / 体感地図 / 行動 / トランスクリプトーム
Outline of Research at the Start

私たちは周りの環境や環境変化を正しく認知し、蓄積した記憶情報に基づいて、適切な行動を出力することができる。脳が外部環境の経験とともに成長し、機能を獲得していく過程において、ゲノム情報はどのように役立つか?本研究は神経細胞における動的なRNAメチル化修飾が環境依存的な翻訳応答とシナプスの機能制御に関与し、認知・感情・行動に変容をもたらす新たな遺伝子発現制御層について検証し、神経科学の理解と精神医学への新しいアプローチを提示することを目指す。

Outline of Final Research Achievements

A human can accurately recognize his/her surrounding environment and environmental changes. This capability is gained through accumulated experience and memory, producing appropriate actions to the ever-changing environment. We hypothesized that RNA m6A modification plays a role in activity-dependent neural development by controlling the structure and function of the cytoskeleton in an activity-dependent manner. We further reasoned that such a function can be mediated by local translation at the neuronal microtubule ends during neurodevelopment. Using imaging analysis in genetically modified animals and cultured cells, we found that RNA m6A modification is essential for the expression of the RNA-binding protein APC, which is necessary for the transport of mRNA in axons, and its deficiency affects the dynamic control of microtubules and axon growth. Furthermore, we discovered that gene mutations associated with autism affect this pathway.

Academic Significance and Societal Importance of the Research Achievements

脳の発達には環境との相互作用が必須であるが、基本的なメカニズムが明らかになっていない。神経細胞における局所翻訳がシナプスの機能に大きな役割を果たしているため、環境依存的回路形成に深く関わると推測できるが、詳細な制御機構が明らかではない。一方、“Epitranscriptome”はRNA化学修飾の全貌を表す「オーム」として2017年に確立され、個体発生、癌、肥満、神経科学など多くの生命分野に寄与してきた。脳の病気と特に関連すると考えられているが、その作動メカニズムに不明点が多い。本研究はその関連性について検証した結果、RNA修飾によるタンパク質の発現制御が軸索の成長に関わることを明らかにした。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (16 results)

All 2024 2023 2022 2021

All Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (7 results) (of which Int'l Joint Research: 7 results,  Invited: 7 results)

  • [Journal Article] epidecodeR: a functional exploration tool for epigenetic and epitranscriptomic regulation2024

    • Author(s)
      Joshi Kandarp、Wang Dan O
    • Journal Title

      Briefings in Bioinformatics

      Volume: 25 Issue: 2

    • DOI

      10.1093/bib/bbad521

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I2023

    • Author(s)
      Wu Hao、Li Ying、Zhang Qian、Wang Hanxun、Xiu Wenyu、Xu Pu、Deng Yujie、Huang Wanxu、Wang Dan Ohtan
    • Journal Title

      Cell Death & Disease

      Volume: 14 Issue: 1

    • DOI

      10.1038/s41419-023-05581-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RNA G-quadruplex organizes stress granule assembly through DNAPTP6 in neurons2023

    • Author(s)
      Asamitsu Sefan、Yabuki Yasushi、Matsuo Kazuya、Kawasaki Moe、Hirose Yuki、Kashiwazaki Gengo、Chandran Anandhakumar、Bando Toshikazu、Wang Dan Ohtan、Sugiyama Hiroshi、Shioda Norifumi
    • Journal Title

      Science Advances

      Volume: 9 Issue: 8

    • DOI

      10.1126/sciadv.ade2035

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long-lasting housing environment manipulation and acute loss of environmental enrichment impact BALB/c mice behaviour in multiple functional domains2022

    • Author(s)
      Sukegawa, M., Yoshihara, T., Hou, S., Asano, M., Hannan., AJ. and Wang, DO.
    • Journal Title

      European Journal of Neuroscience

      Volume: 55 Issue: 5 Pages: 1118-1140

    • DOI

      10.1111/ejn.15602

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] pSNAP: Proteome-wide analysis of elongating nascent polypeptide chains2022

    • Author(s)
      Uchiyama Junki、Roy Rohini、Wang Dan Ohtan、Morikawa Kazuya、Kawahara Yuka、Iwasaki Mio、Yoshino Chiaki、Mishima Yuichiro、Ishihama Yasushi、Imami Koshi
    • Journal Title

      iScience

      Volume: 25 Issue: 7 Pages: 104516-104516

    • DOI

      10.1016/j.isci.2022.104516

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues2022

    • Author(s)
      Yu Peng、Zhou Siting、Gao Yan、Liang Yu、Guo Wenbing、Wang Dan Ohtan、Ding Shuaiwen、Lin Shuibin、Wang Jinkai、Cun Yixian
    • Journal Title

      Genomics, Proteomics & Bioinformatics

      Volume: 21 Issue: 4 Pages: 834-849

    • DOI

      10.1016/j.gpb.2022.07.006

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The m6A-methylome in major depression: A bioinformatic analysis of publicly available datasets2022

    • Author(s)
      Joshi Kandarp、Wang Dan Ohtan、Gururajan Anand
    • Journal Title

      Psychiatry Research Communications

      Volume: 2 Issue: 4 Pages: 100089-100089

    • DOI

      10.1016/j.psycom.2022.100089

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatic RNA adduction derived from metabolic activation of retrorsine in vitro and in vivo2022

    • Author(s)
      Li Weiwei、Cheng Ting、Jiang Tingting、Zhou Mengyue、Gong Bowen、Zhao Guode、Li Jing、Tan Rong、Yang Xiaojing、Joshi Kandarp、Peng Ying、Cheng Maosheng、Liu Ting、Wang Dan Ohtan、Zheng Jiang
    • Journal Title

      Chemico-Biological Interactions

      Volume: 365 Pages: 110047-110047

    • DOI

      10.1016/j.cbi.2022.110047

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of Potent and Selective Inhibitors of Fat Mass Obesity-Associated Protein Using a Fragment-Merging Approach2021

    • Author(s)
      Prakash Muthuraj、Itoh Yukihiro、Fujiwara Yoshie、Takahashi Yukari、Takada Yuri、Mellini Paolo、Elboray Elghareeb E.、Terao Mitsuhiro、Yamashita Yasunobu、Yamamoto Chika、Yamaguchi Takao、Kotoku Masayuki、Kitao Yuki、Singh Ritesh、Roy Rohini、Obika Satoshi、Oba Makoto、Wang Dan Ohtan、Suzuki Takayoshi
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 64 Issue: 21 Pages: 15810-15824

    • DOI

      10.1021/acs.jmedchem.1c01107

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] m6A RNA modification and its reader proteins at neuronal synapses2023

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      Jacque Monod Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] m6A RNA modification and its reader proteins at neuronal synapses2023

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      Neurochemistry Society
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] m6A RNA modification and its reader proteins at neuronal synapses2023

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      FAOP meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] m6A RNA modification and its reader proteins at neuronal synapses2023

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      46th JNS meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] m6A RNA modification and its reader proteins at neuronal synapses2023

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      2nd CJK meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] m6A and its reader proteins at the synapses2022

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      Molecular and Cellular Cognition Society Meeting (Melbourne)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] m6A and its reader proteins at the synapses2022

    • Author(s)
      Dan Ohtan Wang
    • Organizer
      The 44th Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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