Translational regulation enhances distinction of cell types in the nervous system

Abstract

Multicellular organisms are composed of specialized cells with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains to be understood. In this study, by performing RNA-seq and ribo-seq in genetically-defined cells in the Drosophila brain, we revealed substantial posttranscriptional regulations that augment the cell-type distinctions. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias towards the 5′ untranslated regions (UTR) in glia. Using a transgenic reporter, we provide evidence that the UTR confer translational suppression selectively in glia. Overall, these findings underscore the profound impact of translational regulation in shaping cell identity and provide new insights into the molecular mechanisms driving cell-type diversity.