| 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.
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