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Analyses of physiological functions of super-disordered proteins

Research Project

Project/Area Number 21K19246
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
Research InstitutionHokkaido University

Principal Investigator

Nakagawa Shinichi  北海道大学, 薬学研究院, 教授 (50324679)

Co-Investigator(Kenkyū-buntansha) 泊 幸秀  東京大学, 定量生命科学研究所, 教授 (90447368)
Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords超天然変性タンパク質 / 変異マウス / 胎生致死 / ゲノム編集 / 相分離 / 天然変性領域
Outline of Research at the Start

これまでの分子生物学では、タンパク質の機能はアミノ酸の一次配列によって決められており、特定の配列を持つタンパク質は特定の立体構造へと折りたたまれ、その立体構造によって決められる特異的な相互作用がそれぞれの機能を決めていると考えられてきました。ところが最近になって、ゲノムの中には全長に渡って特定の立体構造をとりにくい配列を持つ「超天然変性タンパク質」が多数存在しており、それらは既知の機能ドメインを全く持たないにもかかわらず、重要な分子機能を持つことが明らかとなってきています。本研究では、これらの超天然変性タンパク質の変異マウスをゲノム編集の技術を用いて作製し、その生理機能を明らかにします。

Outline of Final Research Achievements

It has long been thought that the function of a protein is determined by its specific three-dimensional structure. However, it is becoming clear that there are many "intrinsically disordered proteins" within the genome, which have sequences that make it difficult to adopt a specific structure throughout their entire length. These proteins lack any known functional domains, making it impossible to predict what physiological functions they perform. Therefore, in this study, we created mutant mice lacking these functionally uncharacterized intrinsically disordered proteins to investigate their physiological roles. As a result, we found that mutations in at least four types of these proteins cause embryonic lethality, indicating that they perform crucial physiological functions.

Academic Significance and Societal Importance of the Research Achievements

様々な生物のゲノム配列が明らかとなるにつれて、生物を作るためのパーツの記載は終了した、これからはシステムを理解する時代だ、と言われるようになりました。ところが、ゲノムの中には配列からは機能を予測することが出来ないタンパク質がまだまだ残されています。我々はそれらの中でも特に特定の立体構造を取りにくいタンパク質を「超天然変性タンパク質」と呼んでいますが、今回の研究で、それらのタンパク質にも重要な生理機能があることが明らかとなりました。今後はこれら超天然変性タンパク質の機能を理解し、さらに応用へとつなげることで、従来型のタンパク質では不可能であった新たな分子操作技術の開発が期待されます。

Report

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

    (10 results)

All 2023 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Nondomain biopolymers: Flexible molecular strategies to acquire biological functions2023

    • Author(s)
      Arakawa K, Hirose T, Inada T, Ito T, Kai T, Oyama M, Tomari Y, Yoda T, Nakagawa S.
    • Journal Title

      Genes to Cells

      Volume: 28 Issue: 8 Pages: 539-552

    • DOI

      10.1111/gtc.13050

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The cell type‐specific ER membrane protein UGS148 is not essential in mice2021

    • Author(s)
      Takahashi Osamu、Tanahashi Mayuko、Yokoi Saori、Kaneko Mari、Yanaka Kaori、Nakagawa Shinichi、Maita Hiroshi
    • Journal Title

      Genes to Cells

      Volume: 27 Issue: 1 Pages: 43-60

    • DOI

      10.1111/gtc.12910

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ArcRNAs and the formation of nuclear bodies.2021

    • Author(s)
      Shinichi Nakagawa, Tomohiro Yamazaki, Taro Mannen, Tetsuro Hirose
    • Journal Title

      Mammalian Genome

      Volume: - Issue: 2 Pages: 382-401

    • DOI

      10.1007/s00335-021-09881-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Hero11 is a novel nucleolar disordered protein essential for mouse development2023

    • Author(s)
      Riko Okabe, Kotaro Tsuboyama, Yukihide Tomari, and Shinichi Nakagawa
    • Organizer
      RNA 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hero11 is a novel nucleolar disordered protein essential for mouse development2023

    • Author(s)
      Riko Okabe, Kotaro Tsuboyama, Yukihide Tomari, and Shinichi Nakagawa
    • Organizer
      RNA granule meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「非ドメイン型」バイオポリマーの生物学2022

    • Author(s)
      中川 真一
    • Organizer
      第6回クマムシ学研究会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Biology of "nondomain" biopolymers2022

    • Author(s)
      Shinichi Nakagawa
    • Organizer
      Kumamoto liaison lab seminar
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Biology of "nondomain" biopolymers2022

    • Author(s)
      Shinichi Nakagawa
    • Organizer
      RIKEN BIE workshop
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Physiological analyses of super-disordered proteins mutant mice2022

    • Author(s)
      Shinichi Nakagawa
    • Organizer
      第95回日本生化学会年会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] A super-disordered protein Hero11 is a novel ucleolar component essential in mice2022

    • Author(s)
      Riko Okabe, Kotaro Tsuboyama, Yukihide Tomari, and Shinichi Nakagawa
    • Organizer
      CSHL ASIA
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-07-13   Modified: 2025-01-30  

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