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Protein translation rate determines neocortical neuron fate

Author

Listed:
  • Ekaterina Borisova

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Andrew G. Newman

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Marta Couce Iglesias

    (Max Planck Institute for Molecular Genetics)

  • Rike Dannenberg

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Theres Schaub

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Bo Qin

    (Max Planck Institute for Molecular Genetics)

  • Alexandra Rusanova

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    Research Institute of Medical Genetics)

  • Marisa Brockmann

    (Charité-Universitätsmedizin Berlin)

  • Janina Koch

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Marieatou Daniels

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Paul Turko

    (Charité-Universitätsmedizin Berlin)

  • Olaf Jahn

    (Max Planck Institute for Multidisciplinary Sciences
    University Medical Center Göttingen, Georg-August-University)

  • David R. Kaplan

    (University of Toronto)

  • Marta Rosário

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Takao Iwawaki

    (Kanazawa Medical University)

  • Christian M. T. Spahn

    (Charité-Universitätsmedizin Berlin)

  • Christian Rosenmund

    (Charité-Universitätsmedizin Berlin)

  • David Meierhofer

    (Max Planck Institute for Molecular Genetics)

  • Matthew L. Kraushar

    (Max Planck Institute for Molecular Genetics)

  • Victor Tarabykin

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Mateusz C. Ambrozkiewicz

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

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.

Suggested Citation

  • Ekaterina Borisova & Andrew G. Newman & Marta Couce Iglesias & Rike Dannenberg & Theres Schaub & Bo Qin & Alexandra Rusanova & Marisa Brockmann & Janina Koch & Marieatou Daniels & Paul Turko & Olaf Ja, 2024. "Protein translation rate determines neocortical neuron fate," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49198-w
    DOI: 10.1038/s41467-024-49198-w
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    References listed on IDEAS

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