Elucidation for the mechanism of gene expression control specific for prokaryote(Fostering Joint International Research)
Project/Area Number |
16KK0166
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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Allocation Type | Multi-year Fund |
Research Field |
Structural biochemistry
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Research Institution | Kyushu University (2019) National Institute of Advanced Industrial Science and Technology (2016-2017) |
Principal Investigator |
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Project Period (FY) |
2017 – 2019
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
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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.
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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.
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Report
(2 results)
Research Products
(4 results)
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[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.
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Journal Title
Nature Communications
Volume: 10
Issue: 1
Pages: 1501-1501
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Molecular Immunology
Volume: 116
Pages: 199-207
DOI
Related Report
Peer Reviewed
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