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. By performing RNA-seq and Ribo-seq from genetically labelled cell types in Drosophila, we profiled the transcriptome and translatome of neuronal and glial cells in the brain. This comparative profiling revealed substantial posttranscriptional regulation of protein expression. We further found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low especially in glia, leading to preferential translation in neurons. Notably, the distribution of ribosome footprints on these mRNAs exhibited a remarkable bias towards the 5′ untranslated regions (UTR) in glial cells. Using a transgenic reporter system, 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.