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Timed global reorganization of protein synthesis during neocortex neurogenesis at codon resolution

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Title:Timed global reorganization of protein synthesis during neocortex neurogenesis at codon resolution
Creators Name:Harnett, D. and Ambrozkiewicz, M.C. and Zinnall, U. and Borisova, E. and Rusanova, A. and Dannenberg, R. and Imami, K. and Münster-Wandowski, A. and Fauler, B. and Mielke, T. and Selbach, M. and Landthaler, M. and Spahn, C.M.T. and Tarabykin, V. and Ohler, U. and Kraushar, M.L.
Abstract:Translation modulates the timing and amplification of gene expression after transcription. Development of the brain’s neocortex requires precisely timed and spatially targeted gene expression, but the relationship between mRNA vs. protein synthesis throughout the genome is unknown. We perform a comprehensive analysis of the reactants, synthesis, and products of mRNA translation spanning mouse neocortex neurogenesis. Ribosome number in the cortical plate decreases sharply at mid-neurogenesis during a transition in neuronal subtype specification, shifting the fundamental kinetics of protein synthesis, with mRNA and protein levels frequently divergent. Satb2, which drives an essential neuronal subtype-specific program, is a highly dynamically translated mRNA with surprisingly broad transcription across diverse neuronal lineages. Satb2 protein achieves its neuronal subtype expression through timed regulation by the RNA-binding protein Pumilio2. Thus, the refinement of transcriptional programs by protein synthesis is a widespread feature of neuronal specification. Developmental neocortex translatome data are provided in an open-source resource: https://shiny.mdc-berlin.de/cortexomics/.
Keywords:Animals, Mice
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2021.06.23.449626
Date:24 June 2021
Official Publication:https://doi.org/10.1101/2021.06.23.449626

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