| Project/Area Number |
22KF0399
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| Project/Area Number (Other) |
21F51085 (2021-2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2021-2022) |
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| Section | 外国 |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
王 丹 (2021, 2023) 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (50615482)
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| Co-Investigator(Kenkyū-buntansha) |
BROIX LOIC 国立研究開発法人理化学研究所, 生命機能科学研究センター, 外国人特別研究員
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| Host Researcher |
王 丹 (2022) 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (50615482)
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| Foreign Research Fellow |
BROIX LOIC 国立研究開発法人理化学研究所, 生命機能科学研究センター, 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2023: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2022: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2021: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | microtubule / N6-methyl-adenosine / cytoskeleton / YTHDF1 / beta actin / axon development / axon / growth cone / m6A signals |
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| Outline of Research at the Start |
神経細胞は、樹状突起や軸索が細胞本体から遠くまで伸びているのが特徴で、高度に発達した細胞です。その発生過程で神経細胞は、mRNAを神経突起に沿って送り、局所翻訳を行うことで、細胞内コンパートメントのプロテオームを空間的・時間的に制御しています。本研究は、軸索の発達、シナプスの恒常性、神経回路の発達など、さまざまな神経細胞の機能においてRNA化学修飾の機能を解明する。
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| Outline of Annual Research Achievements |
Subcellular mRNA localization and local translation are crucial for spatially regulated gene expression in neurons. However, the precise mechanisms regulating the selective transport and translation of mRNAs contributing to processes such as axonal growth and branching are only partially understood. Here, we present evidence of N6-methyladenosine (m6A)-mediated translational control of the RNA-binding protein, APC, influencing cytoskeletal dynamics at the growth cone. Our findings demonstrate that m6A modifications occur on Apc mRNA, with subsequent recognition and binding by YTHDF1 to promote APC translation in neuronal somata. Moreover, we observe that disrupting the m6A pathway interferes with the transport and local translation of β-actin mRNA in the axon and growth cone, a deficit that can be rescued by the exogenous expression of APC protein in cultured neurons. Furthermore, we show that YTHDF1 is required for the development of axons in callosal projection neurons in vivo during cortical development. Our findings suggest a novel mechanism involving m6A-mediated regulation of APC protein translation, linking epitranscriptomics to axonal mRNA targeting, cytoskeletal dynamics, and axon development.
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