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.
Significance Statement: Despite sharing the same genome, diverse cell types in our body exhibit distinct functions and morphologies. This cellular diversity arises from the synthesis of differential sets of proteins. While transcriptional controls of gene expression have been extensively studied, the role of translational regulations in cell-type specialization remains underinvestigated. Here, we examined the contribution of these two steps to cellular heterogeneity in the fruit fly brain by comparing mRNA expression (transcriptome) and ribosome distribution on mRNA (translatome). Our dataset provides compelling evidence that cell-type distinctions in the transcriptomes are further augmented at the level of mRNA translation. Our findings thus shed light on the previously unexplored role of translational regulations in shaping cell type diversity.
Competing Interest Statement
The authors have declared no competing interest.
