2019 Fiscal Year Final Research Report
Elucidation of the molecular mechanism of disease development by disruption of RNA metabolism
| Project/Area Number |
16H05154
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
花田 礼子 大分大学, 医学部, 教授 (00343707)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | RNA / 希少疾患 / 遺伝性神経変性疾患 / RNA代謝 / 動物疾患モデル |
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| Outline of Final Research Achievements |
In this study, we investigated the molecular mechanism of neurodegeneration involving tRNA metabolism and the function of a novel RNA kinase molecule, NOL9. In vitro and in vivo analysis of various tRNA fragments, which have been reported to cause neuronal cell death, revealed that 5'Tyr-tRF derived from tyrosine tRNA induces p53-dependent neuronal cell death. In vitro kinase assays using the mouse fibroblasts or recombinant proteins produced by a cell-free protein expression system were performed for NOL9. However, no kinase activity was observed in NOL9 molecules, which was surprisingly different from previous reports.
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| Free Research Field |
生化学、分子生物学、分子遺伝学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において、チロシンtRNAから生じるsmall RNAが神経細胞死を惹起し、神経変性疾患の原因になることを示した。また、このsmall RNAはPKM2を結合することでPKM2自体の機能やそれが関与するシグナル伝達機構に影響を及ぼす可能性がある。このように、新たな希少難治性疾患の分子病態メカニズムが明らかになったことで、治療創薬につながる可能性が示された。また、新たな神経細胞死の病態メカニズムが明らかになったことで、高齢社会で社会問題となっているパーキンソン病やアルツハイマー病に対する新たな治療につながる可能性がある。
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