| Project/Area Number |
21K19050
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 37:Biomolecular chemistry and related fields
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| Research Institution | Kyushu University (2022-2024)
Osaka University (2021) |
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Principal Investigator |
Murata Asako 九州大学, 総合理工学研究院, 准教授 (50557121)
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| Project Period (FY) |
2021-07-09 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | RNA / 立体構造解析 / 低分子化合物 |
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| Outline of Research at the Start |
本研究は、低分子NA(Naphthyridine Azaquinolone)で誘起される新奇RNA立体構造の実証を目的とする。本研究の目的達成のために、NAと標的RNAとの結合評価、および、種々の構造解析手法を用いたNA-標的RNA複合体の立体構造解析を行う。さらに、NAで誘起される新奇RNA立体構造の、RNA編集反応における反応活性制御への応用を検討する。
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| Outline of Final Research Achievements |
The aim of this study was to elucidate novel RNA conformations induced by the small molecule NA (Naphthyridine Azaquinolone). Our previous work identified a specific RNA sequence-structural motif targeted by NA. In this study, we investigated the interaction between NA and this RNA motif using surface plasmon resonance, thermal melting analysis, and mass spectrometry. We found that a 3-base × 3-base internal loop with the sequence 5´-AUA-3´/5´-A(C/U)G-3´ is crucial for NA binding. Additionally, we determined the solution structure of the NA-RNA complex by NMR spectroscopy. The findings in this study provide molecular-level insight into RNA-small molecule recognition and underscore the potential of NA as a scaffold for designing RNA-targeted small molecules.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、低分子NA（Naphthyridine Azaquinolone）によって誘起される新奇RNA立体構造を実証した。NAと標的RNAとの結合様式を各種手法により詳細に解析し、さらにNMR解析によりNA-RNA複合体の立体構造を明らかにした。本研究の成果は、低分子NAのRNA標的分子としての新たな応用可能性を示すとともに、RNA標的低分子創薬におけるケミカルスペースの拡大に貢献するものである。
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