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Elucidating the importance of HuR and identifing novel regulatory factor in innate immune system-regulating mechanisms

Research Project

Project/Area Number 17K15726
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionNara Institute of Science and Technology

Principal Investigator

ORI Daisuke  奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (70709287)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords自然免疫 / 炎症 / RNA結合タンパク質 / 転写後調節 / 免疫学
Outline of Final Research Achievements

Although previous research in our laboratory indicated that HuR positively regulated anti-viral responses, detailed mechanisms have been still unknown. In this research, we revealed that HuR stabilized Plk2 mRNA through 4th one of four AU-rich element in Plk2 mRNA 3’-untranslated region, resulting in the promotion of anti-viral responses by indirectly and positively regulating nuclear translocation of IRF3.
Furthermore, we identified two candidate genes which may be involved in the regulation of innate immune responses by performing CRISPR/Cas9 system-based screening focusing on RNA-binding proteins. Currently, we are generating and analyzing genetically modified mice to clarify the physiological importance of these two genes.

Academic Significance and Societal Importance of the Research Achievements

HuRの抗ウイルス応答調節機構の解析は、感染症に対する免疫機構の新たな一面を明らかにしたものである。また将来、感染症の治療あるいは免疫応答制御において、新たな標的メカニズムとして重要な意味を持つと考えている。
さらに、スクリーニングにより自然免疫応答の新規調節因子の候補として2種のタンパク質を同定できたが、当該タンパク質と免疫機構との関連を示す報告はほとんどない。そのため、これらのタンパク質の機能を詳細に明らかにすることで、自然免疫応答の未解明の調節機構の同定に繋がり、調節機構の包括的理解や自己炎症性疾患などの病態理解や予防などに繋がるのもであると確信している。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (5 results) Book (2 results)

  • [Journal Article] PtdIns3P phosphatases MTMR3 and MTMR4 negatively regulate innate immune responses to DNA through modulating STING trafficking2019

    • Author(s)
      Putri DDP, Kawasaki T, Murase M, Sueyoshi T, Deguchi T, Ori D, Suetsugu S, Kawai T.
    • Journal Title

      J Biol Chem

      Volume: - Issue: 21 Pages: 8412-8423

    • DOI

      10.1074/jbc.ra118.005731

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sensing Self and Non-Self DNA by Innate Immune Receptors and Their Signaling Pathways.2018

    • Author(s)
      Sok SPM, Ori D, Nagoor NH, Kawai T.
    • Journal Title

      Crit Rev Immunol.

      Volume: 38 Issue: 4 Pages: 279-301

    • DOI

      10.1615/critrevimmunol.2018026540

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hu Antigen R Regulates Antiviral Innate Immune Responses through the Stabilization of mRNA for Polo-like Kinase 2.2018

    • Author(s)
      Sueyoshi T, Kawasaki T, Kitai Y, Ori D, Akira S, Kawai T.
    • Journal Title

      J Immunol.

      Volume: 200 Issue: 11 Pages: 3814-3824

    • DOI

      10.4049/jimmunol.1701282

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs2017

    • Author(s)
      Yoshinaga Masanori、Nakatsuka Yoshinari、Vandenbon Alexis、Ori Daisuke、Uehata Takuya、Tsujimura Tohru、Suzuki Yutaka、Mino Takashi、Takeuchi Osamu
    • Journal Title

      Cell Reports

      Volume: 19 Issue: 8 Pages: 1614-1630

    • DOI

      10.1016/j.celrep.2017.05.009

    • NAID

      120006305989

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Regnase-1 and Regnase-3 regulate cell fate of early lymphoid progenitors in the bone marrow2018

    • Author(s)
      Takuya Uehata, Daisuke Ori, Masaki Miyazaki, Hiroshi Kawamoto, Osamu Takeuchi
    • Organizer
      The 47th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Inhibition of NLRP3 inflammasome-mediated IL-1β release by 1’-acetoxychavicol acetate (ACA), a gingerderived compound2018

    • Author(s)
      Sophia Ping Meow Sok, Daisuke Ori, Noor Hasima Nagoor, Taro Kawai
    • Organizer
      The 47th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Elucidation of molecular mechanism of interleukin 33 release2018

    • Author(s)
      Mizuka Nagayama, Takumi Kawasaki, Daisuke Ori, Taro Kawai
    • Organizer
      The 47th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Induction of cell death by imiquimod (R837) and its role in immune responses2017

    • Author(s)
      Haruna Okude, Takumi Kawasaki, Daisuke Ori, Motoya Murase, Ken Ishii and Taro Kawai
    • Organizer
      The 46th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2017 Research-status Report
  • [Presentation] Analysis of cell death pathway induced by innate immune ligands2017

    • Author(s)
      Haruna Okude, Daisuke Ori, Takumi Kawasaki, Motoya Murase and Taro Kawai
    • Organizer
      Consotiam of Biological Sciences 2017
    • Related Report
      2017 Research-status Report
  • [Book] 免疫・炎症病態×治療Update2019

    • Author(s)
      熊ノ郷 淳
    • Total Pages
      252
    • Publisher
      南山堂
    • ISBN
      9784525167813
    • Related Report
      2018 Annual Research Report
  • [Book] 免疫ペディア2017

    • Author(s)
      熊ノ郷 淳
    • Total Pages
      317
    • Publisher
      羊土社
    • ISBN
      9784758120807
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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