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Studies on the functional role of unpaired regions of nucleic acid structures and their effects of molecular crowding

Research Project

Project/Area Number 18K05325
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionKonan University

Principal Investigator

Nakano Shu-ichi  甲南大学, フロンティアサイエンス学部, 教授 (70340908)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsDNA二重鎖 / グアニン四重鎖 / ハンマーヘッドリボザイム / 一本鎖ループ / 塩基性タンパク質 / テトラアルキルアンモニウムイオン / ポリアミン / 分子クラウディング / シトシン四重鎖 / キメラ核酸 / アルキルアンモニウム / DNA四重鎖 / テトラペンチルアンモニウムイオン / グアニン四重鎖結合タンパク質 / DNA四重鎖構造 / RGG配列ペプチド / DNAループ / 熱安定性 / 生体ポリアミン / DNA非標準構造 / ジアミン化合物 / DNA / RNA / 構造安定性
Outline of Final Research Achievements

This study investigates the influences of intracellular crowding environments on nucleic acid structures with unpaired regions. We constructed in vitro experimental systems of intracellular media by using various types of organic compounds and proteins, and investigated DNA and RNA oligonucleotide structures and their thermodynamic stability under the conditions. It was shown that bulky cationic molecules, such as large tetraalkylammonium ions and basic proteins, preferentially interact with long unpaired nucleotides in DNA duplex and quadruplex structures and they can greatly stabilize the structures with long loops. Large tetraalkylammonium ions were also found to enable to enhance the turnover activity of hammerhead ribozymes and to induce topological changes of certain G-quadruplexes. We propose functional roles of unpaired regions in the formation of nucleic acid structures in the presence of high concentrations of bulky cationic molecules.

Academic Significance and Societal Importance of the Research Achievements

カチオン性の有機化合物とタンパク質が大量に存在する分子環境は、核酸の構造形成、とくに長鎖ループ部位を有する非標準構造の形成に大きな影響を与えることを明らかにした。この知見は、細胞内部のクラウディング環境では核酸の非構造部位がこれまで考えられてきた以上に重要な役割をもつことを示唆している。本研究の成果は、核酸の構造と機能に関する分子クラウディング研究を進展させるとともに、細胞内の核酸構造の解明や機能性核酸の開発に役立つデータとしても有意義である。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (6 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Book (1 results) Remarks (4 results)

  • [Journal Article] Evaluation of weak interactions of proteins and organic cations with DNA duplex structures2022

    • Author(s)
      R. Morimoto, M. Horita, D. Yamaguchi, H. Nakai, and S. Nakano
    • Journal Title

      Biophys. J.

      Volume: 121 Issue: 15 Pages: 2873-2881

    • DOI

      10.1016/j.bpj.2022.07.003

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 核酸医薬の効果に影響する細胞内物質のin vitro評価2022

    • Author(s)
      中野修一
    • Journal Title

      Precision Medicine

      Volume: 5 Pages: 64-67

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Enhancement of the catalytic activity of hammerhead ribozymes by organic cations2021

    • Author(s)
      S. Nakano, H. Yamashita, and N. Sugimoto
    • Journal Title

      ChemBioChem

      Volume: 22 Issue: 17 Pages: 2721-2728

    • DOI

      10.1002/cbic.202100280

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 核酸医薬の配列設計のためのin vitro評価:細胞内物質との弱い相互作用の影響2021

    • Author(s)
      中野修一
    • Journal Title

      BIO Clinica

      Volume: 12 Pages: 82-84

    • Related Report
      2021 Research-status Report
  • [Journal Article] 細胞の内部環境は核酸医薬に用いられるオリゴヌクレオチドにどのような影響を与えるか2020

    • Author(s)
      中野修一
    • Journal Title

      月刊細胞

      Volume: 52 Pages: 42-44

    • Related Report
      2020 Research-status Report
  • [Journal Article] Stabilization of DNA loop structures by large cations2019

    • Author(s)
      S. Nakano, T. Ayusawa, Y. Tanino, and N. Sugimoto
    • Journal Title

      J. Phys. Chem. B

      Volume: 123 Issue: 36 Pages: 7687-7694

    • DOI

      10.1021/acs.jpcb.9b06074

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] DNAの構造遷移を促進する物質の探索2022

    • Author(s)
      梅野光莉、橋本留奈、中野修一
    • Organizer
      第45回分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 細胞内分子環境は不安定なDNA四重鎖の形成に有利に働く2021

    • Author(s)
      梅野光莉、宮嵜光一、林花莉、中野修一
    • Organizer
      第44回分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] What effects does intracellular environment have on nucleic acid structures?2021

    • Author(s)
      Shu-ichi Nakano
    • Organizer
      Pacifichem2021(環太平洋国際化学会議)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 塩基性タンパク質を含む分子クラウディング環境におけるDNA四重鎖構造の安定化2020

    • Author(s)
      宮嵜光一、田辺一也、林花梨、武本満理奈、橋本留奈、梅野光莉、中野修一
    • Organizer
      第43回分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Stabilization of Noncanonical DNA Structures in the Presence of Bulky Cations2019

    • Author(s)
      Shu-ichi Nakano, Masao Horita, Kazuya Tanabe, Ryuta Morimoto, Naoki Sugimoto
    • Organizer
      Commemorative International Symposium of the Japan Society of Nucleic Acids Chemistry (CISNAC2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞内分子環境が核酸の構造と機能に与える影響―モデル実験系を用いた解析2019

    • Author(s)
      中野修一
    • Organizer
      新学術領域「分子夾雑の生命化学」第2回関東地区シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 細胞内分子環境がDNA四重鎖の形成に与える影響:モデル実験系による検討2019

    • Author(s)
      田辺和也、森田紗奈、橋本留奈、中野修一
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] カチオン性分子による不安定なDNA四重鎖構造の安定化2018

    • Author(s)
      森田紗奈、中野修一
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Influence of intracellular conditions on DNA and RNA: Insights from model studies2018

    • Author(s)
      Shu-ichi Nakano
    • Organizer
      Konan Research Summit
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 化学と工業(題「分子夾雑環境が制御する核酸分子の機能」)2019

    • Author(s)
      中野修一、杉本直己
    • Total Pages
      3
    • Publisher
      日本化学会
    • Related Report
      2019 Research-status Report
  • [Remarks] 甲南大学フロンティアサイエンス学部バイオ分子機能研究室

    • URL

      https://www.konan-u.ac.jp/hp/FIRST_bmflab/

    • Related Report
      2022 Annual Research Report 2019 Research-status Report
  • [Remarks] 甲南大学バイオ分子機能研究室ホームページ

    • URL

      https://www.konan-u.ac.jp/hp/FIRST_bmflab/index.html

    • Related Report
      2021 Research-status Report
  • [Remarks] バイオ分子機能研究室

    • URL

      https://www.konan-u.ac.jp/hp/FIRST_bmflab/

    • Related Report
      2020 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.konan-u.ac.jp/hp/FIRST_bmflab/

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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