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

Authors

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

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 03 Jul 2026.

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