Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan; Graduate School of Life Sciences, Tohoku University, Sendai, Japan
Faculty of Advanced Engineering, Tokyo University of Sciences, Tokyo, Japan
Mai Kanno
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan; Graduate School of Life Sciences, Tohoku University, Sendai, Japan
RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan
Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically defined cells in the Drosophila brain, we here revealed substantial post-transcriptional regulations that augment the cell-type distinctions at the level of protein expression. 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 their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias toward the 5′ leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open-reading frames in the 5’ leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.
