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2023 年度 実績報告書

軸索とシナプス形成時において細胞骨格を動的に制御するRNAメチル化修飾の役割

研究課題

研究課題/領域番号 22KF0399
配分区分基金
研究機関国立研究開発法人理化学研究所

研究代表者

王 丹  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)

研究分担者 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
研究期間 (年度) 2023-03-08 – 2024-03-31
キーワードmicrotubule / N6-methyl-adenosine / cytoskeleton / YTHDF1 / beta actin / axon development
研究実績の概要

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.

  • 研究成果

    (1件)

すべて 2024

すべて 雑誌論文 (1件)

  • [雑誌論文] m6A RNA methylation-dependent APC translation is required for local translation of b-actin and axon development2024

    • 著者名/発表者名
      Loic Broix, Rohini Roy, Ikumi Oomoto, Hiroki Umeshima, Dan Ohtan Wang
    • 雑誌名

      bioRxiv

      巻: - ページ: -

    • DOI

      10.1101/2020.11.14.382556

URL: 

公開日: 2024-12-25  

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