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Creation of RNA aptamers aiming at the creation of new antifungal drug

Research Project

Project/Area Number 16K14652
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical genome science
Research InstitutionKindai University

Principal Investigator

FUJIWARA Toshinobu  近畿大学, 薬学部, 教授 (80362804)

Research Collaborator YAMASAKI manabu  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsRNAアプタマー / 抗真菌 / 抗真菌薬
Outline of Final Research Achievements

Using the fungal capping enzymes Ceg1, Cet1 and Cet1 mutants that can not bind to Ceg1, we show that nuclear translocation signals are present only in Cet1, and that Ceg1 can not translocate to the nucleus without binding to Cet1. Furthermore, we demonstrate that Cet1 and Ceg1 bind in the cytoplasm, and that the Cet1-Ceg1 complex translocates to the nucleus. Moreover, genetic studies using yeast show that Cet1 and Ceg1 binding is essential for fungal growth. These data indicate that inhibition of Cet1-Ceg1 binding may be the mechanism of action of novel antifungal agents. Then, we obtained the aptamers that selectively inhibit the capping reaction of budding yeast that has been used as a model so far.

Academic Significance and Societal Importance of the Research Achievements

真菌と哺乳類とで異なる反応経路をとるmRNAのcapping反応に着目し、真菌のcapping反応のみを阻害するRNAアプタマーの創製を試みた。その結果、Cet1-Ceg1結合阻害が新規抗真菌薬の作用機序となりうる事が示し、これまでにモデルとした出芽酵母のcapping反応を選択的に阻害するアプタマーを取得している。また、今後作動性が確認されたRNAアプタマーはそれ自身を修飾すること、またはその構造を解析することによる新規化合物のスクリーニングにより、抗真菌薬開発に応用可能である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (25 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Remarks (2 results)

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

    • Related Report
      2018 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
    • 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
    • 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] 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 Research-status Report
    • Peer Reviewed
  • [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] High affinity RNA for capping enzyme of Saccharomyces cerevisiae2016

    • Author(s)
      Yuka Yamada, Manabu Yamasaki, Naoki Takizawa, Akira Fukao, Toshinou Fujiwara
    • Organizer
      12th International Congress on Protein Phosphatase (ICPP12)
    • Place of Presentation
      大阪府東大阪市近畿大学11月ホール
    • Year and Date
      2016-10-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [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
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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