2020 Fiscal Year Final Research Report
Development of the inhibitors to RNA demethylases and it's application to monitor local demethylation
| Project/Area Number |
18K05435
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 38030:Applied biochemistry-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | RNAの脱メチル化 / 阻害剤 / 細胞膜透過性 |
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| Outline of Final Research Achievements |
RNA modification is one of the translational regulation mechanisms which allow cells to respond quickly to stimulations from environment. To study if activity dependent demethylation of reversible m6A modification on mRNAs occurs during local translation at synapse, we planned to obtain the demethylase inhibitor with high cell permiability. We developed FTO inhibitor based on a known compound, and confirmed that it works in cells. On the other hand, we found several compounds which show inhibitory activity by screening, but now, their specificity to two demethylases, FTO and ALKBH5, belonging to the same superfamily is low. Docking simulation suggested key amino acids for further improvement of the inhibitor. At the same time, we prepared FTO-KO and ALKBH5-KO cell lines. Further research is required to examine local demethylation. The FTO inhibitor we developed can be used for the examination of local demethylation in future.
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| Free Research Field |
分子生物学、生化学
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| Academic Significance and Societal Importance of the Research Achievements |
RNA修飾は細胞機能の発現と関係し、パターンやバランスが崩れると、疾患の原因になることもある。本研究で開発したFTO特異的阻害剤は、神経細胞のみならず、各種細胞へ利用が可能である。
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