Cited by 98Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationRNA and protein synthesis mechanisms

An eIF4E1/4E-T Complex Determines the Genesis of Neurons from Precursors by Translationally Repressing a Proneurogenic Transcription Program

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Yang, Guang, Smibert, Craig A., Kaplan, David R., Miller, Freda D.·2014·Neuron

Abstract

Here, we have addressed the mechanisms that determine genesis of the correct numbers of neurons during development, focusing on the embryonic cortex. We identify in neural precursors a repressive complex involving eIF4E1 and its binding partner 4E-T that coordinately represses translation of proteins that determine neurogenesis. This eIF4E1/4E-T complex is present in granules with the processing body proteins Lsm1 and Rck, and disruption of this complex causes premature and enhanced neurogenesis and neural precursor depletion. Analysis of the 4E-T complex shows that it is highly enriched in mRNAs encoding transcription factors and differentiation-related proteins. These include the proneurogenic bHLH mRNAs, which colocalize with 4E-T in granules and whose protein products are aberrantly upregulated following knockdown of eIF4E, 4E-T, or processing body proteins. Thus, neural precursors are transcriptionally primed to generate neurons, but an eIF4E/4E-T complex sequesters and represses translation of proneurogenic proteins to determine appropriate neurogenesis.

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Crossref · 10.1016/j.neuron.2014.10.022

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Authors
Yang, G., Smibert, C. A., Kaplan, D. R., & Miller, F. D.
Affiliations
  • Hospital for Sick Children (CA)
  • University of Toronto (CA)
Corresponding author
  • Kaplan, David R.
  • Miller, Freda D.
Venue
Neuron
Publisher
Elsevier BV
Published
2014-11
Volume
84
Issue
4
Pages
723-739
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2085367342
Cited by
98
References
30
Citations by year
2026: 2 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 13 · 2019: 10 · 2018: 3 · 2017: 10 · 2016: 10 · 2015: 8 · 2014: 1
FWCI
3.36
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • Canadian Institutes of Health Research (125945_1)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
eIF4E1, translation repression, neurogenesis, neuronal precursors, embryonic cortex, P-bodies, LSM1, bHLH transcription factors, neuronal differentiation, mRNA granules
MeSH terms
Animals, Humans, Neurons, Transcription, Genetic, Nucleocytoplasmic Transport Proteins, Eukaryotic Initiation Factor-4E, Mice, Neurogenesis, HEK293 Cells

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