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Visualization of specific RNA secondary structures in vivo

Research Project

Project/Area Number 20K15417
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionInstitute of Physical and Chemical Research (2021-2022)
Kumamoto University (2020)

Principal Investigator

Asamitsu Sefan  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, 訪問研究員 (70849091)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsRNA高次構造 / 神経細胞 / 分子プローブ / マウス脳 / 中枢神経 / 核酸高次構造 / グアニン四重鎖 / グアニン四重鎖(G4) / G4RNAプローブ / RNAターゲティング
Outline of Research at the Start

生体内のRNAは多様な高次構造をとることが知られている。特にグアニンを豊富に含む配列において、非常に安定な4本の鎖からなる四重鎖構造(G4RNA)が形成されることが明らかになっており、RNAプロセシング・翻訳プロセスの多様性に影響を与える因子であることが示唆されてきた。一方で、G4RNAは遺伝子疾患・神経疾患の病態に関与することも指摘されているが、神経機能に与える影響の大部分は未だ解明されていない。本研究課題では、神経細胞で形成されるG4RNAの同定とその細胞内動態からの理解を目的とし、遺伝子工学的応用可能な特定G4RNAを追跡するプローブの開発とマウス脳組織への応用を実施する。

Outline of Final Research Achievements

In this research project, to elucidate the molecular neuroscience role of the G-quadruplex (G4) structure, which is formed by sequences rich in contiguous guanines, we developed a molecular probe that can detect the G4 structure and analyzed the functions using mouse brain and primary mouse neurons. We found that messenger RNA containing the G4 structure tends to accumulate in stress granules, intracellular phase-separating compartments, by various molecular biological analyses using novel peptide probes based on single-stranded antibodies that recognize the G4 structure. Biochemical and electrophysiological analyses revealed that the G4 structure is essential for the formation of functional stress granules and plays an important role in the maintenance of neuronal homeostasis under oxidative stress.

Academic Significance and Societal Importance of the Research Achievements

G4構造は、細胞内の局所環境の変化・化学修飾・相互作用因子等、多くの要因によってダイナミックな形成挙動を示す。本研究によって得られた知見を加味すると、G4構造を足掛かりとする緻密なRNA制御機構がストレス顆粒を含む多くの細胞内相分離体の機能的な形成に貢献することが示唆された。またストレス顆粒は筋萎縮性側索硬化症(ALS)等の神経変性疾患の発症要因と密接に関与している。本研究成果はストレスが関与する多くの疾患の治療薬開発の一助となることが期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (15 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Oxford(英国)

    • Related Report
      2022 Annual Research Report
  • [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
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Small molecule-based detection of non-canonical RNA G-quadruplex structures that modulate protein translation2022

    • Author(s)
      Yousuke Katsuda, Shin-ichi Sato, Maimi Inoue, Hisashi Tsugawa, Takuto Kamura, Tomoki Kida, Rio Matsumoto, Sefan Asamitsu, Norifumi Shioda, Shuhei Shiroto, Yoshiki Oosawatsu, Kenji Yatsuzuka, Yusuke Kitamura, Masaki Hagihara, Toshihiro Ihara and Motonari Uesugi
    • Journal Title

      Nucleic Acids Research

      Volume: 50 Issue: 14 Pages: 8143-8153

    • DOI

      10.1093/nar/gkac580

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Strong and Specific Recognition of CAG/CTG Repeat DNA (5’‐dWGCWGCW‐3’) by a Cyclic Pyrrole‐Imidazole Polyamide2021

    • Author(s)
      Hirose Yuki、Ohno Tomo、Asamitsu Sefan、Hashiya Kaori、Bando Toshikazu、Sugiyama Hiroshi
    • Journal Title

      ChemBioChem

      Volume: 23 Issue: 2

    • DOI

      10.1002/cbic.202100533

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential roles of G-quadruplex structures in RNA granules for physiological and pathological phase separation2021

    • Author(s)
      Asamitsu Sefan、Shioda Norifumi
    • Journal Title

      The Journal of Biochemistry

      Volume: mvab018 Issue: 5 Pages: 527-533

    • DOI

      10.1093/jb/mvab018

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor/ataxia syndrome2021

    • Author(s)
      Asamitsu Sefan、Yabuki Yasushi、Ikenoshita Susumu、Kawakubo Kosuke、Kawasaki Moe、Usuki Shingo、Nakayama Yuji、Adachi Kaori、Kugoh Hiroyuki、Ishii Kazuhiro、Matsuura Tohru、Nanba Eiji、Sugiyama Hiroshi、Fukunaga Kohji、Shioda Norifumi
    • Journal Title

      Science Advances

      Volume: 7 Issue: 3

    • DOI

      10.1126/sciadv.abd9440

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Toward elucidating roles for RNA G-quadruplexes in neurons2022

    • Author(s)
      Sefan Asamitsu
    • Organizer
      8th International Meeting on Quadruplex Nucleic Acids
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経細胞におけるグアニン四重鎖の役割2022

    • Author(s)
      朝光 世煌
    • Organizer
      FIBER 核酸化学ユニバースRising Stars
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] RNA G-quadruplex organizes stress granule assembly through DNAPTP6 in neurons2022

    • Author(s)
      Sefan Asamitsu
    • Organizer
      Functional Genomics in Future
    • Related Report
      2022 Annual Research Report
  • [Presentation] 神経細胞におけるグアニン四重鎖RNA構造の相分離現象に与える影響2022

    • Author(s)
      朝光 世煌、川嵜 萌、廣瀬 優希、矢吹 悌、柏﨑 玄伍、Anandhakumar Chandran、板東 俊和、杉山 弘、塩田 倫史
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 神経細胞におけるRNAグアニン四重鎖構造の役割の解明2021

    • Author(s)
      朝光 世煌、川嵜 萌、柏﨑 玄伍、Anandhakumar Chandran、杉山 弘、矢吹 悌、塩田 倫史
    • Organizer
      日本ケミカルバイオロジー学会第15回年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 神経細胞におけるグアニン四重鎖RNA構造の相分離現象への寄与2021

    • Author(s)
      朝光 世煌、川嵜 萌、廣瀬 優希、矢吹 悌、柏﨑 玄伍、Anandhakumar Chandran、板東 俊和、杉山 弘、塩田 倫史
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Book] Quadruplex Nucleic Acids As Targets For Medicinal Chemistry- Chapter Three - Telomeric quadruplexes as therapeutic targets2020

    • Author(s)
      Sefan Asamitsu, Norifumi Shioda, Hiroshi Sugiyama
    • Total Pages
      546
    • Publisher
      ELSEVIER
    • ISBN
      9780128210178
    • Related Report
      2020 Research-status Report
  • [Book] Development of Selective DNA-Interacting Ligands2020

    • Author(s)
      Sefan Asamitsu
    • Total Pages
      111
    • Publisher
      Springer
    • ISBN
      9789811577161
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] リピート結合剤2020

    • Inventor(s)
      塩田倫史, 矢吹悌, 朝光世煌, 杉山弘, 板東俊和, 池田修司
    • Industrial Property Rights Holder
      塩田倫史, 矢吹悌, 朝光世煌, 杉山弘, 板東俊和, 池田修司
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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