| Project/Area Number |
17K08677
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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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| Research Field |
Pathological medical chemistry
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大塚 哲 金沢医科大学, 総合医学研究所, 准教授 (40360515)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Y14 / Magoh / リン酸化 / ゲノム編集 / 核小体 / Y14(RBM8A) / mRNA / EJC / TAR症候群 / RNA結合因子 |
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| Outline of Final Research Achievements |
Deficient expression of Y14 (RBM8A) gene is known to be a cause of radial defect thrombocytopenia (TAR syndrome). In this study, we reported that the phosphorylation control of two serines in Y14 is involved in nuclear localization. Furthermore, it was revealed that Magoh, which stably binds to Y14 intracellularly, contributes to the intracellular stability of each. In addition, localization analysis of Y 14 was performed at the electron microscope level. We proposed a method to observe the structure of mRNA from its co-localization with the mRNA binding factor Upf2. Furthermore, we have established an inducible expression system for phosphorylated mutants and a genome editing mouse strain, and are continuing to analyze their roles at the cell and animal level.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者のオリジナルなY14のリン酸化研究をもとに、核内で作られたmRNAが、膜で仕切られていない核小体へ混入させない仕組みと欠損の影響を分子レベルで提案できた点に学術的な意義がある。本研究では、RNAの分解経路や中心体と関連させて研究されてきたY14について、これまで予想もされていなかった機能を核小体への局在と関連させて初めて明らかにすることに従来の研究にはない特色があった。さらに、TAR症候群の発症機序解明に有用なヒト細胞系およびマウスモデル系を提供し、細胞死に隠されていた未知のY14の機能とTAR症候群における病態との関係を解き明かすことができた点にも意義がある。
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