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A new genetic tool for translational regulation in mammalian cells

Research Project

Project/Area Number 17K19200
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry and related fields
Research InstitutionKyoto University

Principal Investigator

SATO SHINICHI  京都大学, 化学研究所, 准教授 (70534478)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsリボスイッチ / RNA / 核酸 / タンパク質翻訳制御
Outline of Final Research Achievements

Riboswitch is a naturally occurring sensor that is directly involved in regulating its own activity, in response to the concentrations of its specific ligand. In this project, we designed a new split-RNA system that permits gene expression control in mammalian cells. The split RNA consists of two pieces of RNA segments, which are practically dissected internal ribosome entry site (IRES), and the RNA serves as a translational ON/OFF regulator as it reassembles or disassembles the IRES segments in cells. One piece of the IRES segments can be transfected as a switch lever for regulating translation of gene of interests, followed by the other IRES segment. We have successfully observed the fact that the expression of luciferase proteins, used as reporter genes, was induced by the split-IRES-based riboswitch in mammalian cells.

Academic Significance and Societal Importance of the Research Achievements

細胞のタンパク質発現を自在に操ることができる技術は,細胞機能の理解や人為的制御に有効な手段となり得る.近年,様々な人工リボスイッチが開発され,その成果が学術雑誌に報告されているが,その多くは単純な翻訳制御システムを持つ原核細胞のタンパク質発現を制御するものである.従って,研究ツールとしての応用範囲は限定的であった.本研究では,複雑なタンパク質発現システムを持つ真核細胞で機能する高性能リボスイッチの開発に成功した.その学術的意義は高い.また,本研究成果は,RNA構造体を分割する大胆かつ斬新な核酸設計を行っており,今後の核酸設計に新たな指針を与えるなど,基礎研究においても大きなインパクトを生む.

Report

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

    (15 results)

All 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (11 results)

  • [Journal Article] Multifunctionalization of Cells with a Self-Assembling Molecule to Enhance Cell Engraftment2019

    • Author(s)
      Takashima Ippei、Kusamori Kosuke、Hakariya Hayase、Takashima Megumi、Vu Thi Hue、Mizukami Yuya、Noda Naotaka、Takayama Yukiya、Katsuda Yousuke、Sato Shin-ichi、Takakura Yoshinobu、Nishikawa Makiya、Uesugi Motonari
    • Journal Title

      ACS Chemical Biology

      Volume: 14 Issue: 4 Pages: 775-783

    • DOI

      10.1021/acschembio.9b00109

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Live-cell imaging of multiple endogenous mRNAs permits the direct observation of RNA granule dynamics2018

    • Author(s)
      Yatsuzuka Kenji、Sato Shin-ichi、Pe Kathleen Beverly、Katsuda Yousuke、Takashima Ippei、Watanabe Mizuki、Uesugi Motonari
    • Journal Title

      Chemical Communications

      Volume: 54 Issue: 52 Pages: 7151-7154

    • DOI

      10.1039/c8cc03805h

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemical decontamination of iPS cell-derived neural cell mixtures2018

    • Author(s)
      Mao Di、Chung Xie Khim Watson、Andoh-Noda Tomoko、Qin Ying、Sato Shin-ichi、Takemoto Yasushi、Akamatsu Wado、Okano Hideyuki、Uesugi Motonari
    • Journal Title

      Chem Commun (Camb). 1355

      Volume: 54 Issue: 11 Pages: 1355-1358

    • DOI

      10.1039/c7cc08686e

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Method for Imaging Live-Cell RNA Using an RNA Aptamer and a Fluorescent Probe2018

    • Author(s)
      Sato Shin-ichi、Yatsuzuka Kenji、Katsuda Yousuke、Uesugi Motonari
    • Journal Title

      Methods Mol Biol.

      Volume: 1649 Pages: 305-318

    • DOI

      10.1007/978-1-4939-7213-5_20

    • ISBN
      9781493972128, 9781493972135
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] RNA高次構造構築による新規遺伝子発現制御法の開発2019

    • Author(s)
      勝田 陽介・佐藤 慎一・嘉村 匠人・北村 裕介・萩原 正規・井原 敏博
    • Organizer
      日本化学会第99春季年会2019
    • Related Report
      2018 Annual Research Report
  • [Presentation] G-quadruplexを利用したRNA fraction検出法の開発2019

    • Author(s)
      勝田 陽介, 嘉村匠人, 北村裕介, 萩原正規, 佐藤慎一, 井原 敏博
    • Organizer
      日本分析化学会第67年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] RNA G-quadruplex形成を利用した新規遺伝子発現抑制技術の開発2018

    • Author(s)
      勝田 陽介, 嘉村匠人, 北村裕介, 萩原正規, 佐藤慎一, 井原 敏博
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] RNA高次構造の形成誘導を利用した 遺伝子機能解析技術の開発2018

    • Author(s)
      嘉村匠人, 勝田陽介, 北村裕介, 萩原正規, 佐藤慎一, 井原敏博
    • Organizer
      第36回九州分析化学若手の会夏季セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小分子を用いたRNA四重鎖構造の網羅的探索2018

    • Author(s)
      井上 舞美、勝田 陽介、北村 裕介、上杉 志成、 萩原 正規、佐藤 慎一、井原 敏博
    • Organizer
      第36回九州分析化学若手の会夏季セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] 外的因子によるRNA高次構造の形成誘導および遺伝子発現制御2018

    • Author(s)
      嘉村匠人、勝田陽介、北村裕介、萩原正規、佐藤慎一、井原敏博
    • Organizer
      第30回生体機能関連化学若手の会サマースクール
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小分子を用いたタンパク質翻訳反応制御機能を有するRNA高次構造の網羅的探索2018

    • Author(s)
      井上 舞美、勝田 陽介、北村 裕介、上杉 志成、萩原 正規、佐藤 慎一、井原 敏博
    • Organizer
      第30回生体機能関連化学若手の会サマースクール
    • Related Report
      2018 Annual Research Report
  • [Presentation] RNAを標的とした新規機能解析技術の開発2018

    • Author(s)
      嘉村匠人、勝田陽介、北村裕介、萩原正規、佐藤慎一、井原敏博
    • Organizer
      化学関連支部合同九州大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小分子を用いたRNA四重鎖構造の網羅的探索2018

    • Author(s)
      井上 舞美、勝田 陽介、北村 裕介、上杉 志成、萩原 正規、佐藤 慎一、井原 敏博
    • Organizer
      化学関連支部合同九州大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] がん関連遺伝子を対象とした 細胞内RNA G-quadruplexの網羅的探索2018

    • Author(s)
      勝田 陽介, 佐藤 慎一, 井上 舞美, 嘉村 匠人, 北村 裕介, 萩原 正規,上杉 志成, 井原 敏博
    • Organizer
      日本ケミカルバイオロジー学会第13回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Live-Cell Multi-Color Imaging of Endogenous RNAs with a Small Molecule and a Short RNA2018

    • Author(s)
      YATSUZUKA, Kenji; SATO, Shin-ichi; PE, Kathleen Beverly; UESUGI, Motonari
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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