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Translational regulation enhances distinction of cell types in the nervous system

View ORCID ProfileToshiharu Ichinose, View ORCID ProfileShu Kondo, Mai Kanno, View ORCID ProfileYuichi Shichino, View ORCID ProfileMari Mito, View ORCID ProfileShintaro Iwasaki, View ORCID ProfileHiromu Tanimoto
doi: https://doi.org/10.1101/2023.06.15.545207
Toshiharu Ichinose
1Frontier Research Institute for Interdisciplinary Sciences, Tohoku University
2Graduate School of Life Sciences, Tohoku University
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  • For correspondence: [email protected] [email protected]
Shu Kondo
3Faculty of Advanced Engineering, Tokyo University of Sciences
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Mai Kanno
2Graduate School of Life Sciences, Tohoku University
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Yuichi Shichino
4RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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Mari Mito
4RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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Shintaro Iwasaki
4RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
5Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan
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Hiromu Tanimoto
2Graduate School of Life Sciences, Tohoku University
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  • For correspondence: [email protected] [email protected]
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Abstract

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 posttranscriptional 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 towards the 5′ leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open reading frames (uORFs) 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Competing Interest Statement: The authors declare no competing interest.

  • Figure 5 and the corresponding text were revised.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 01, 2024.
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Translational regulation enhances distinction of cell types in the nervous system
Toshiharu Ichinose, Shu Kondo, Mai Kanno, Yuichi Shichino, Mari Mito, Shintaro Iwasaki, Hiromu Tanimoto
bioRxiv 2023.06.15.545207; doi: https://doi.org/10.1101/2023.06.15.545207
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Translational regulation enhances distinction of cell types in the nervous system
Toshiharu Ichinose, Shu Kondo, Mai Kanno, Yuichi Shichino, Mari Mito, Shintaro Iwasaki, Hiromu Tanimoto
bioRxiv 2023.06.15.545207; doi: https://doi.org/10.1101/2023.06.15.545207

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