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bioRxiv · 10.64898/2026.06.28.734671

Activity-dependent synthesis of translational machinery through dynamic remodeling of ribonucleoprotein granules

Ichinose, T.·Kanno, M.·Makino, T.·Shichino, Y.·Iwasaki, S.·Tanimoto, H.
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Abstract

Neuronal stimulation drives gene-expression programs supporting long-lasting changes, yet how depolarization reshapes post-transcriptional regulation remains poorly understood. Here, we combined optogenetic stimulation with neuron-specific Ribo-seq and RNA-seq in the Drosophila brain to resolve activity-evoked translational dynamics. Stimulation triggered two temporally ordered programs: a rapid wave to translate synapse remodeling factors and neuropeptides, followed by a dominant delayed program that selectively upregulated translation of protein synthesis machinery, including nearly all cytosolic ribosomal proteins (RPs). Transcripts in the late program are marked by 5 terminal oligopyrimidine (TOP) motifs. TOP mRNAs accumulated in ribonucleoprotein granules at the basal state but are released upon stimulation. We identified La-related protein as a key regulator of the activity-dependent translation of TOP mRNA and memory consolidation. Comparative genomics indicated that TOP enrichment in RP mRNAs is specific to metazoans. These findings suggest that animals acquired activity-dependent TOP-mRNA control to couple neuronal stimulation with adaptation of translational capacity.

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Ichinose, T., Kanno, M., Makino, T., Shichino, Y., Iwasaki, S., Tanimoto, H.. 2026-07-02. Activity-dependent synthesis of translational machinery through dynamic remodeling of ribonucleoprotein granules. https://doi.org/10.64898/2026.06.28.734671

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