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Elucidation of the operation principle of the translation repression by microRNA machinery in human

Publicly Offered Research

Project AreaNeo-taxonomy of noncoding RNAs
Project/Area Number 17H05607
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKindai University

Principal Investigator

藤原 俊伸  近畿大学, 薬学部, 教授 (80362804)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
KeywordsmiRNA作動原理 / 翻訳制御 / RNA-タンパク質複合体(RNP) / microRNA / RNA結合タンパク質 / mRNA-タンパク質複合体(mRNP) / mRNA分解 / miRNA
Outline of Annual Research Achievements

miRNAは、Agoタンパク質と複合体(miRISC)を形成し、標的mRNAのpoly(A)鎖の分解と翻訳抑制という二つの経路を介して、遺伝子発現を抑制する。我々は、miRNAによる翻訳開始抑制時に、翻訳開始過程のどのステップが標的とされているのか、またどのような因子を標的としているのかを、ヒト培養細胞抽出液を用いた独自のin vitro翻訳系およびmRNA-タンパク質複合体(mRNP)pull-down法を用いて解析した。そして、miRNA存在下においては、翻訳開始複合体eIF4Fの構成因子であるeIF4A(eIF4AI、eIF4AII)が、eIF4F複合体から除外されていることを直接的に証明している。しかしながら、miRNA反応マシナリーがどのようにしてeIF4Aを翻訳開始複合体より解離させているのかについては依然不明である。
我々はこれまでに、CCR4-NOT複合体の構成因子がmiRNAに誘導される翻訳開始抑制にどのように寄与するかを、各構成因子のノックアウトMEF(Mouse Embryonic Fibroblast)細胞を用いて解析を進めてきた。その結果、TNRC6タンパク質のmiRNAによる翻訳抑制への寄与をはじめ、これまで報告されてきたCCR4-NOT複合体を中心とする分子機構では説明がつかない結果を得たので報告する。さらに、ヒト培養細胞抽出液によるin vitro翻訳系を用いたmRNA pull-down法により、miRISCが形成された標的mRNA上のみに存在するタンパク質を精製し、質量分析によりmiRISCによる翻訳抑制に必要であると考えられる因子Xを同定した。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (39 results)

All 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (27 results) (of which Int'l Joint Research: 11 results,  Invited: 9 results) Remarks (2 results)

  • [Int'l Joint Research] University Medical Center Hamburg(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Center for Molecular Neurobiology (ZMNH)(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] McGill University(カナダ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Emerging Evidence of Translational Control by AU-Rich Element-Binding Proteins2019

    • Author(s)
      Otsuka Hiroshi、Fukao Akira、Funakami Yoshinori、Duncan Kent E.、Fujiwara Toshinobu
    • Journal Title

      Frontiers in Genetics

      Volume: 10 Pages: 322-322

    • DOI

      10.3389/fgene.2019.00332

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of matrix metalloproteinase 9-interacting sequences in staphylococcal superantigen-like protein 5.2018

    • Author(s)
      Kohno K, Itoh S, Hanai A, Takii T, Fujiwara T, Onozaki K, Tsuji T, Hida S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 497(2) Issue: 2 Pages: 713-718

    • DOI

      10.1016/j.bbrc.2018.02.138

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function2018

    • Author(s)
      Yamaguchi Tomokazu et al
    • Journal Title

      Science Signaling

      Volume: 11 Issue: 516 Pages: 3638-3638

    • DOI

      10.1126/scisignal.aan3638

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Translation of Hepatitis A Virus IRES Is Upregulated by a Hepatic Cell-Specific Factor2018

    • Author(s)
      Sadahiro Akitoshi、Fukao Akira、Kosaka Mio、Funakami Yoshinori、Takizawa Naoki、Takeuchi Osamu、Duncan Kent E.、Fujiwara Toshinobu
    • Journal Title

      Frontiers in Genetics

      Volume: 9 Pages: 1-10

    • DOI

      10.3389/fgene.2018.00307

    • NAID

      120006534584

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The coupled- and uncoupled mechanisms by which trans-acting factors regulate mRNA stability and translation2017

    • Author(s)
      Fukao, A., and Fujiwara, T.
    • Journal Title

      The Journal of Biochemistry

      Volume: 161 Pages: 309-314

    • DOI

      10.1093/jb/mvw086

    • NAID

      40021219745

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F62017

    • Author(s)
      Igarashi Masayuki、Sawa Ryuichi、Yamasaki Manabu、Hayashi Chigusa、Umekita Maya、Hatano Masaki、Fujiwara Toshinobu、Mizumoto Kiyohisa、Nomoto Akio
    • Journal Title

      The Journal of Antibiotics

      Volume: 70 Issue: 5 Pages: 582-589

    • DOI

      10.1038/ja.2016.161

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatial regulation of the KH domain RNA-binding protein Rnc1 mediated by a Crm1-independent nuclear export system in Schizosaccharomyces pombe.2017

    • Author(s)
      Satoh R, Matsumura Y, Tanaka A, Takada M, Ito Y, Hagihara K, Inari M, Kita A, Fukao A, Fujiwara T, Hirai S, Tani T, Sugiura R.
    • Journal Title

      Mol Microbiol.

      Volume: 104 Issue: 3 Pages: 428-448

    • DOI

      10.1111/mmi.13636

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 細胞・組織特異性を規定するリボソーム結合因子を介した転写後制御機構2018

    • Author(s)
      藤原俊伸
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 哺乳類におけるmiRISCによる翻訳抑制機構の解明2018

    • Author(s)
      坂村由梨佳、友廣拓生、大塚衆志、深尾亜喜良、船上仁範、鈴木亨、山本雅、藤原俊伸
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ポリオウイルス組織特異性を生み出す,IRES依存的翻訳制御機構の解析2018

    • Author(s)
      石田一希、貞廣暁利、安達俊吾、深尾亜喜良、船上仁範、夏目徹、藤原俊伸
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] New insights into CCR4-Not deadenylase complex function in microRNA-mediated gene silencing2018

    • Author(s)
      Yurika Sakamura、Takumi Tomohiro、Hiroshi Otsuka、Akira Fukao、Kent E Duncan、Toshinobu Fujiwara
    • Organizer
      The complex life of RNA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ARE binding protein ZFP36L1 represses translation via CCR4-NOT complex independently of RNA degradation machinery2018

    • Author(s)
      Hiroshi Otsuka、Akira Fukao、Kent E Duncan、Toshinobu Fujiwara
    • Organizer
      Translational Control
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] New insights into CCR4-Not deadenylase complex function in microRNA-mediated gene silencing2018

    • Author(s)
      Akira Fukao、Takumi Tomohiro、Yurika Sakamura、Hiroshi Otsuka、Kent E Duncan、Yukihide Tomari、Toshinobu Fujiwara
    • Organizer
      Translational Control
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ARE binding protein ZFP36L1 represses translation via CCR4-NOT complex independently of RNA degradation machinery2018

    • Author(s)
      Toshinobu Fujiwara
    • Organizer
      ELAVENICE 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ARE結合タンパク質AUF1による遺伝子発現制御機構の解析2018

    • Author(s)
      深尾亜喜良、西阪皓理、松木香菜子、大塚衆志、船上仁範、藤原俊伸
    • Organizer
      第20回日本RNA学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ZFP36L1による脱アデニル化非依存的な翻訳抑制の解析2018

    • Author(s)
      大塚衆志、深尾亜喜良、船上仁範、藤原俊伸
    • Organizer
      第20回日本RNA学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] MicroRNAを介した遺伝子サイレンシングにおけるCCR4‐NOT脱アデニル化酵素複合体の機能解析2018

    • Author(s)
      友廣拓生、坂村由梨佳、大塚衆志、深尾亜喜良、鈴木亨、山本雅、泊幸秀、藤原俊伸
    • Organizer
      第20回日本RNA学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 哺乳類におけるmiRISCによる翻訳抑制機構の新たな知見2018

    • Author(s)
      坂村由梨佳、友廣拓生、大塚衆志、深尾亜喜良、船上仁範、鈴木亨、山本雅、足立俊吾、夏目徹、藤原俊伸
    • Organizer
      第20回日本RNA学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ポリオウイルス組織特異性を生み出すIRES依存的翻訳制御機構の解析2018

    • Author(s)
      石田一希、貞廣暁利、安達俊吾、深尾亜喜良、船上仁範、夏目徹、藤原俊伸
    • Organizer
      第20回日本RNA学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A型肝炎ウイルスIRES依存的翻訳は肝臓特異的因子により活性化される.2018

    • Author(s)
      貞廣暁利、深尾亜喜良、小坂実央、滝沢直己、船上仁範、竹内理、Kent E Duncan、藤原俊伸
    • Organizer
      第20回日本RNA学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ZFP36L1 represses translation initiation independently of deadenylation mediated by AU-Rich elements2018

    • Author(s)
      Hiroshi Otsuka、Akira Fukao、Kent E Duncan、Toshinobu Fujiwara
    • Organizer
      FASEB Science Research Conferences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] New insights into CCR4-Not deadenylase complex function in microRNA-mediated gene silencing2018

    • Author(s)
      Takumi Tomohiro、Yurika Sakamura、Hiroshi Otsuka、Akira Fukao、Kent E Duncan、Toshinobu Fujiwara
    • Organizer
      FASEB Science Research Conferences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 非典型的な翻訳開始機構から見えてきた巧妙なタンパク質合成制御機構2018

    • Author(s)
      藤原俊伸
    • Organizer
      第6回CCR4-NOT研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Poliovirusの組織特異的増殖を生み出すIRES特異的翻訳機構の解明2017

    • Author(s)
      藤原俊伸
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ZFP36L1 represses translation initiation independently of deadenylation mediated by AU-RICH element2017

    • Author(s)
      Toshinobu Fujiwara
    • Organizer
      Cutting Edge Developments in RNA Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ZFP36L1 represses translation initiation independently of deadenylation mediated by AU-RICH element2017

    • Author(s)
      Fukao A, Otsuka H, Funakami Y, Duncan K, Fujiwara T
    • Organizer
      EMBO Conference Protein Synthesis and Translational Control
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidation of elementary processes in which RNA-Binding protein HuD2017

    • Author(s)
      Otsuka H, Fukao A, Funakami Y, Duncan K, Fujiwara T
    • Organizer
      EMBO Conference Protein Synthesis and Translational Control
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analyses of cell type specific translation from IRES mRNA derived from two different poliovirus strains2017

    • Author(s)
      Sadahiro A, Fukao A, Duncan K, Takeuchi O, Fujiwara T
    • Organizer
      RNA 2017 (The 22nd Annual Meeting of the RNA Society)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The novel function of PABP interacting protein 1 (Paip 1) in translation initiation2017

    • Author(s)
      Aoyama T, Fukao A, Sonenberg N, Fujiwara T
    • Organizer
      RNA 2017 (The 22nd Annual Meeting of the RNA Society)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 哺乳類におけるmiRISCによる翻訳抑制機構の解明2017

    • Author(s)
      坂村由梨佳、友廣拓生、大塚衆志、深尾亜喜良、船上仁範、鈴木亨、山本雅、藤原俊伸
    • Organizer
      第19回日本RNA学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] KH型RNA結合タンパク質Rnc1のRae1依存的な核外輸送を介したMAPKシグナル制御機構2017

    • Author(s)
      佐藤亮介、萩原可奈子、深尾亜喜良、藤原俊伸、平井晋哉、谷時雄、杉浦麗子
    • Organizer
      第19回日本RNA学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] in vitro翻訳システムを用いたmiRNAによる翻訳制御分子機構の解析2017

    • Author(s)
      深尾亜喜良、友廣拓生、大塚衆志、青山智彦、船上仁範、足達俊吾、夏目徹、藤原俊伸
    • Organizer
      第19回日本RNA学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ARE 結合タンパク質AUF1による遺伝子発現制御機構の解析2017

    • Author(s)
      西阪皓理、松木香菜子、大塚衆志、深尾亜喜良、船上仁範、藤原俊伸
    • Organizer
      第19回日本RNA学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] BRF1によるmRNA分解と共役した翻訳抑制機構の解析2017

    • Author(s)
      大塚衆志、武知美和、深尾亜喜良、船上仁範、藤原俊伸
    • Organizer
      第19回日本RNA学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Remarks] 近畿大学薬学部生化学研究室

    • URL

      https://www.phar.kindai.ac.jp/biochemistry/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 近畿大学薬学部生化学研究室

    • URL

      http://www.phar.kindai.ac.jp/biochemistry/

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2020-01-20  

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