ArticleNature communications2024
Protein translation rate determines neocortical neuron fate.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Proteomic profile of hippocampal growth cones through early postnatal development.Development (Cambridge, England) · 2026Article
- Data-driven model reveals increased stability of CAG-expanded huntingtin RNA due to MID1 binding.PLoS computational biology · 2026Article
- Encephalopathy-linked UFM1 variants impede neuronal protein translation, development, and function.EMBO molecular medicine · 2026Article
- Structural variations in evolutionary novel genomic regions: new insights into neurodevelopmental disorders by long-read DNA Sequencing.Molecular medicine (Cambridge, Mass.) · 2026Article
- Cell type-specific in vivo proteomes with a multicopy mutant methionyl tRNA synthetase mouse line.Lab animal · 2025Article
- A primer on copper biology in the brain.Neurobiology of disease · 2025Review
- Ribogenesis shaping the brain.Nature cell biology · 2025Article
- Orchestrating Neural Development Through mRNA Translation Regulation.Journal of neurochemistry · 2025Review
- IRE1α promotes phagosomal calcium flux to enhance macrophage fungicidal activity.Cell reports · 2025Article
- Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X.Nature communications · 2025Article
- Cortical projection neurons with distinct axonal connectivity employ ribosomal complexes with distinct protein compositions.bioRxiv : the preprint server for biology · 2025Article
- DEAD/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders.Trends in genetics : TIG · 2025Review
- Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.Molecular biology of the cell · 2025Article
- A subpopulation of cortical neurons altered by mutations in the autism risk gene DDX3X.Biology open · 2025Article
- Understanding ubiquitination in neurodevelopment by integrating insights across space and time.Nature structural & molecular biology · 2025Review
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Authors and funding
21 authors.
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Abstract
The mammalian neocortex comprises an enormous diversity regarding cell types, morphology, and connectivity. In this work, we discover a post-transcriptional mechanism of gene expression regulation, protein translation, as a determinant of cortical neuron identity. We find specific upregulation of protein synthesis in the progenitors of later-born neurons and show that translation rates and concomitantly protein half-lives are inherent features of cortical neuron subtypes. In a small molecule screening, we identify Ire1α as a regulator of Satb2 expression and neuronal polarity. In the developing brain, Ire1α regulates global translation rates, coordinates ribosome traffic, and the expression of eIF4A1. Furthermore, we demonstrate that the Satb2 mRNA translation requires eIF4A1 helicase activity towards its 5'-untranslated region. Altogether, we show that cortical neuron diversity is generated by mechanisms operating beyond gene transcription, with Ire1α-safeguarded proteostasis serving as an essential regulator of brain development.
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