The study used comparative transcriptome-translatome analyses to investigate the impact of translational regulation on cell-type distinctions in the Drosophila brain. Key findings include:
Genome-wide analysis of the whole fly heads revealed substantial post-transcriptional regulation, with many neuronal transcripts showing remarkably low translational efficiency (TE).
Cell-type specific Ribo-seq and RNA-seq, using genetically-tagged ribosomes, showed that the distinction between neuronal and glial cells is much more pronounced at the translational level compared to the transcriptional level.
Neuronal transcripts encoding ion channels, neurotransmitter receptors, and other proteins fundamental to neuronal functions exhibited preferential translation in neurons but translational suppression in glia. This was mediated by the presence of upstream open reading frames (uORFs) in the 5' leaders of these transcripts, which stalled ribosomes in glia.
A transgenic reporter assay confirmed that the 5' leader sequences of a neuronal gene (Rh1) conferred translational suppression specifically in glial cells, and this effect was alleviated by mutating the uORFs.
Overall, the study demonstrates the profound impact of translational regulation in enhancing the proteome diversity between neuronal and glial cells in the Drosophila brain, beyond what is observed at the transcriptional level alone.
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by Ichinose,T.,... at www.biorxiv.org 06-16-2023
https://www.biorxiv.org/content/10.1101/2023.06.15.545207v4Deeper Inquiries