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The architecture of protein synthesis in the developing neocortex at near-atomic resolution reveals Ebp1-mediated neuronal proteostasis at the 60S tunnel exit

Authors :
Thorsten Mielke
Hiroshi Yamamoto
Christian M. T. Spahn
Matthew L. Kraushar
Victor Tarabykin
Ulrike Zinnall
Mladen-Roko Rasin
Paul Turko
Agnieszka Münster-Wandowski
Imre Vida
Dieter Beule
Theres Schaub
Carlos H. Vieira-Vieira
Koshi Imami
Matthias Selbach
Mateusz C. Ambrozkiewicz
Ekaterina Borisova
Dermot Harnett
Ferdinand Krupp
Jörg Bürger
Markus Landthaler
Thiemo Sprink
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

Abstract

SUMMARYProtein synthesis must be finely tuned in the nervous system, as it represents an essential feature of neurodevelopmental gene expression, and dominant pathology in neurological disease. However, the architecture of ribosomal complexes in the developing mammalian brain has not been analyzed at high resolution. This study investigates the architecture of ribosomesex vivofrom the embryonic and perinatal mouse neocortex, revealing Ebp1 as a 60S peptide tunnel exit binding factor at near-atomic resolution by multiparticle cryo-electron microscopy. The impact of Ebp1 on the neuronal proteome was analyzed by pSILAC and BONCAT coupled mass spectrometry, implicating Ebp1 in neurite outgrowth proteostasis, within vivoembryonic Ebp1 knockdown resulting in dysregulation of neurite outgrowth. Our findings reveal Ebp1 as a central component of neocortical protein synthesis, and the 60S peptide tunnel exit as a focal point of gene expression control in the molecular specification of neuronal morphology.Graphical abstract

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....8b405799ecfa5cd5257ef5f8a44b9d90
Full Text :
https://doi.org/10.1101/2020.02.08.939488