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  A critical period of translational control during brain development at codon resolution

Harnett, D., Ambrozkiewicz, M. C., Zinnall, U., Rusanova, A., Borisova, E., Dannenberg, R., et al. (2021). A critical period of translational control during brain development at codon resolution. bioRxiv. doi:10.1101/2021.06.23.449626.

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bioRxiv_Harnett et al_2022.pdf (Preprint), 17MB
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Harnett, Dermot , Author
Ambrozkiewicz, Mateusz C. , Author
Zinnall, Ulrike , Author
Rusanova, Alexandra , Author
Borisova, Ekaterina , Author
Dannenberg, Rike , Author
Imami, Koshi , Author
Münster-Wandowski,, Agnieszka , Author
Fauler, Beatrix1, Author              
Mielke, Thorsten1, Author              
Selbach, Matthias , Author
Landthaler, Markus, Author
Spahn, Christian M. T. , Author
Tarabykin, Victor , Author
Ohler, Uwe, Author
Kraushar, Matthew2, Author              
Affiliations:
1Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              
2High-Resolution Neurogenetics (Matthew Kraushar), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3374910              

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 Abstract: Translation modulates the timing and amplification of gene expression after transcription. Brain development requires uniquely complex gene expression patterns, but large-scale measurements of translation directly in the prenatal brain are lacking. We measure the reactants, synthesis, and products of translation spanning mouse neocortex neurogenesis, and discover a transient window of dynamic regulation at mid-gestation. Timed translation upregulation of chromatin binding proteins like Satb2, which is essential for neuronal subtype differentiation, restricts protein expression in neuronal lineages despite broad transcriptional priming in progenitors. In contrast, translation downregulation of ribosomal proteins sharply decreases ribosome number, coinciding with a major shift in protein synthesis dynamics at mid-gestation. Changing levels of eIF4EBP1, a direct inhibitor of ribosomal protein translation, are concurrent with ribosome downregulation and controls Satb2 fate acquisition during neuronal differentiation. Thus, the refinement of transcriptional programs by translation is central to the molecular logic of brain development. Modeling of the developmental neocortex translatome is provided as an open-source searchable resource: https://shiny.mdc-berlin.de/cortexomics/.

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Language(s): eng - English
 Dates: 2021-11-23
 Publication Status: Published online
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 Identifiers: DOI: 10.1101/2021.06.23.449626
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Title: bioRxiv
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