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Analysis of posttranscriptional mechanisms of Regnase-1-mediated mRNA decay in innate immune system

Research Project

Project/Area Number 25860355
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

MINO Takashi  京都大学, ウイルス研究所, 助教 (60646149)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords自然免疫 / 炎症 / サイトカイン / 転写後調節 / RNA安定性制御 / Regnase-1 / Ribosome / UPF1
Outline of Final Research Achievements

Posttranscriptional regulation that modifies mRNA stability and translation provides rapid and flexible control of gene expression and control of mRNAs stability is important for coordinating the initiation and resolution of inflammation. However, the posttranscriptional mechanisms in innate immunity remain to be clarified. This study is aiming to investigate the posttranscriptional mechanisms in innate immunity based on the roles of an RNase Regnase-1 we identified.In this study, we demonstrate that Regnase-1 localized to cytoplasm and endoplasmic reticulum (ER), but not to PB and SGs, and colocalizes with ribosome. Regnase-1 destabilized translationally active mRNAs and the helicase activity of UPF1 was required for the Regnase-1-mediated mRNA decay, similar to the decay mechanisms of nonsense mRNAs. Our findings reveal that Regnase-1 might function in recognizing the translationally active mRNA and triggering mRNA destabilizing immediately.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (20 results)

All 2015 2014 2013 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] Regnase-1 and Roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms2015

    • Author(s)
      Takashi Mino, Yasuhiro Murakawa, Akira Fukao, Alexis Vandenbon, Hans-Hermann Wessels, Daisuke Ori, Takuya Uehata, Sarang Tartey, Shizuo Akira, Yutaka Suzuki, Carola G. Vinuesa, Uwe Ohler, Daron M. Standley, Markus Landthaler, Toshinobu Fujiwara, Osamu Takeuchi.
    • Journal Title

      Cell

      Volume: XX

    • NAID

      120005608042

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Inhibition of DNA replication of human papillomavirus by using zinc finger-single-chain FokI dimer hybrid2014

    • Author(s)
      Takashi Mino, Tomoaki Mori, Yasuhiro Aoyama, Takashi Sera
    • Journal Title

      Molecular Biotechnology

      Volume: 56 Issue: 8 Pages: 731-737

    • DOI

      10.1007/s12033-014-9751-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex2014

    • Author(s)
      Sarang Tartey, Kazufumi Matsushita, Alexis Vandenbon, Daisuke Ori, Tomoko Imamura, Takashi Mino, Daron M. Standley, Jules A. Hoffmann, Jean-Marc Reichhart, Shizuo Akira, Osamu Takeuchi
    • Journal Title

      The EMBO Journal

      Volume: 33 Issue: 20 Pages: 2332-2348

    • DOI

      10.15252/embj.201488447

    • NAID

      120005649311

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene- and protein-delivered zinc finger–staphylococcal nuclease hybrid for inhibition of DNA replication of human papillomavirus2013

    • Author(s)
      Takashi Mino, Tomoaki Mori, Yasuhiro Aoyama, Takashi Sera
    • Journal Title

      PLoS One

      Volume: 8 Issue: 2 Pages: e56633-e56633

    • DOI

      10.1371/journal.pone.0056633

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Essential Roles of K63-Linked Polyubiquitin-Binding Proteins TAB2 and TAB3 in B Cell Activaion via MAPKs.2013

    • Author(s)
      Ori D
    • Journal Title

      J Immunol

      Volume: 190(8) Issue: 8 Pages: 4037-4045

    • DOI

      10.4049/jimmunol.1300173

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Critical Role of AZI2 in GM-CSF-Induced Dendritic Cell Differentiation2013

    • Author(s)
      Fukasaka M, Ori D, Kawagoe T, Uematsu S, Maruyama K, Okazaki T, Kozaki T, Imamura T, Tartey S, Mino T, Satoh T, Akira S, Takeuchi O
    • Journal Title

      J Immunol

      Volume: 190 Issue: 11 Pages: 5702-11

    • DOI

      10.4049/jimmunol.1203155

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo.2013

    • Author(s)
      Kazuya Masuda, Barry Ripley, Riko Nishimura, Takashi Mino, Osamu Takeuchi, Go Shioi, Hiroshi Kiyonari, and Tadamitsu Kishimoto
    • Journal Title

      Proceeding of the National Academy of Sciences of the United States of America

      Volume: 110 Issue: 23 Pages: 9409-9414

    • DOI

      10.1073/pnas.1307419110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation2013

    • Author(s)
      Uehata T, Iwasaki H, Vandenbon A, Matsushita, K, Hernandez Cuellar E, Kuniyoshi K, Satoh T, Mino T, Suzuki Y, Standley DM, Tsujimura T, Rakugi H, Isaka Y, Takeuchi O and Akira S
    • Journal Title

      Cell

      Volume: 23;153 Issue: 5 Pages: 1036-49

    • DOI

      10.1016/j.cell.2013.04.034

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Post-transcriptional regulation of cytokine mRNA controls the initiation and resolution of inflammation2013

    • Author(s)
      Takashi Mino, Osamu Takeuchi
    • Journal Title

      Biotechnology and Genetic Engineering

      Volume: 29 Issue: 1 Pages: 49-60

    • DOI

      10.1080/02648725.2013.801236

    • NAID

      120005474488

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Regnase-1 destabilizes inflammationrelated mRNAs in a translation-dependent manner2014

    • Author(s)
      Takashi Mino, Osamu Takeuchi
    • Organizer
      2014 Annual Meeting of Japanese Society for Immunology
    • Place of Presentation
      京都府京都市
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] A novel role of Regnase-1 in the iron homeostasis and anemia2014

    • Author(s)
      Masanori Yoshinaga, Takashi Mino, Osamu Takeuchi
    • Organizer
      2014 Annual Meeting of Japanese Society for Immunology
    • Place of Presentation
      京都府京都市
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Regnase-1は翻訳に依存して炎症関連mRNAを分解する2014

    • Author(s)
      三野享史,深尾亜喜良,藤原俊伸,竹内理
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Regnase-1 標的mRNA 配列の網羅的同定2014

    • Author(s)
      阿部壮岐,三野享史,村川泰裕,竹内理
    • Organizer
      RNAフロンティアミーティング2014
    • Place of Presentation
      和歌山県西牟婁郡白浜町
    • Year and Date
      2014-09-16 – 2014-09-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 炎症の転写後調節におけるRegnase-1の作用機構2014

    • Author(s)
      三野享史
    • Organizer
      新学術領域「ゲノム支援」2014年度 拡大班会議
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2014-08-20 – 2014-08-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Regnase-1 destabilizes inflammation-related mRNAs in a translation-dependent manner2014

    • Author(s)
      Takashi Mino, Akira Fukao, Toshinobu Fujiwara, Osamu Takeuchi,
    • Organizer
      RNA 2014 NAGOYA, The 16th RNA meeting of the RNA Society of Japan
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2014-07-23 – 2014-07-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Regnase-1の作用機構から探る自然免疫応答における転写後調節の解明

    • Author(s)
      三野享史
    • Organizer
      新学術領域「ゲノム支援」2013年度 拡大班会議
    • Place of Presentation
      神戸ポートピアホテル(兵庫県神戸市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 自然免疫応答の転写後調節におけるRegnase-1 の作用機構

    • Author(s)
      三野享史
    • Organizer
      名古屋市立大学大学院薬学研究科藤原研究室セミナー
    • Place of Presentation
      名古屋市立大学田辺通キャンパス(愛知県名古屋市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 自然免疫応答の転写後調節におけるRegnase-1 の作用機構

    • Author(s)
      三野享史
    • Organizer
      日本化学会北海道支部 平成25年度室蘭・苫小牧地区化学講演会
    • Place of Presentation
      苫小牧工業高等専門学校(北海道苫小牧市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 京都大学ウイルス研究所感染防御研究分野竹内研究室ホームページ

    • URL

      http://www.virus.kyoto-u.ac.jp/Lab/Takeuchi_HP/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 京都大学ウイルス研究所感染防御研究分野竹内研究室ホームページ

    • URL

      http://www.virus.kyoto-u.ac.jp/Lab/Takeuchi_HP/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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