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Protein translation rate determines neocortical neuron fate

Authors :
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 Jahn
David R. Kaplan
Marta Rosário
Takao Iwawaki
Christian M. T. Spahn
Christian Rosenmund
David Meierhofer
Matthew L. Kraushar
Victor Tarabykin
Mateusz C. Ambrozkiewicz
Source :
Nature Communications, Vol 15, Iss 1, Pp 1-25 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

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.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.66af00ce766642a5b9c7bd2aa0b9eb91
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-024-49198-w