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Elucidation for the mechanism of gene expression control specific for prokaryote(Fostering Joint International Research)

Research Project

Project/Area Number 16KK0166
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionKyushu University (2019)
National Institute of Advanced Industrial Science and Technology (2016-2017)

Principal Investigator

Numata Tomoyuki  九州大学, 農学研究院, 准教授 (10401564)

Project Period (FY) 2017 – 2019
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
KeywordsノンコーディングRNA / リボスイッチ / PreQ1 / 真正細菌 / 遺伝子発現調節 / 低分子合成化合物 / 転写抑制 / 修飾ヌクレオシド / RNA / tRNA修飾 / 合成化合物 / RNAラベリング / 原核生物 / 結晶構造解析 / RNA結合タンパク質 / 分子間相互作用 / RNA分子装置
Outline of Final Research Achievements

Riboswitches are structured RNA elements that typically reside in the 5’-UTRs of bacterial mRNAs, and regulate gene expression by recognizing their cognate ligand. Here, I report the discovery of synthetic small molecules that bind the preQ1 riboswitch and co-crystal structures with the small molecules. A fluorescently labeled preQ1 riboswitch was screened against a small-molecule microarray. Several hits were detected, and the interactions between the riboswitch and these compounds were confirmed. Co-crystal structures with the preQ1 riboswitch showed that dibenzofuran-containing compounds bind the preQ1 binding cleft. In vitro transcription termination assay showed that the dibenzofuran-containing compounds increase transcription termination efficiency, suggesting down-regulation of gene expression in the presence of the compounds. The co-crystal structures are the starting point for developing additional compounds that target the bacteria-specific queuosine biosynthetic pathway.

Academic Significance and Societal Importance of the Research Achievements

PreQ1リボスイッチと結合して下流遺伝子の発現を抑制する低分子合成化合物を取得し,結晶構造解析により両者の相互作用機構を解明した.PreQ1はtRNAの修飾ヌクレオシドの一つであるキューオシンの前駆体である.キューオシンはリボソームが正確にタンパク質を合成するうえで不可欠な修飾ヌクレオシドである.したがって,この低分子化合物がリボスイッチの下流遺伝子の発現を抑制してタンパク質合成に重要なキューオシンの形成を阻害すると考えられる.本成果は,原核生物のRNAを標的とした新たな抗生剤の開発に貢献できると考えられる.

Report

(2 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (4 results)

All 2019 2017

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

  • [Int'l Joint Research] National Institutes of Health(米国)2017

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Synthetic ligands for PreQ1 riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure2019

    • Author(s)
      Connelly, C.M., Numata, T., Boer, R.E., Moon, M.H., Sinniah, R.S., Barchi, J.J., Ferre-D'Amare, A.R., Schneekloth, J.S. Jr.
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1501-1501

    • DOI

      10.1038/s41467-019-09493-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Crystal structure and biochemical characterization of CJP38, a β-1,3-glucanase and allergen of Cryptomeria japonica pollen2019

    • Author(s)
      Takashima, T., Taku, T., Yamanaka, T., Fukamizo, T., Numata, T., Ohnuma, T.
    • Journal Title

      Molecular Immunology

      Volume: 116 Pages: 199-207

    • DOI

      10.1016/j.molimm.2019.10.016

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Crystal structure of the type III CRISPR-Cas Cmr complex bound to a target analog2019

    • Author(s)
      Tomoyuki Numata, Takuo Osawa
    • Organizer
      Thermophiles 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2017-03-15   Modified: 2021-02-19  

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