The P-body protein 4E-T represses translation to regulate the balance between cell genesis and establishment of the postnatal NSC pool

Adelaida Kolaj; Siraj K. Zahr; Beatrix S. Wang; Taylor Krawec; Hilal Kazan; Guang Yang; David R. Kaplan; Freda D. Miller

Cell Reports (Mar 2023)

The P-body protein 4E-T represses translation to regulate the balance between cell genesis and establishment of the postnatal NSC pool

Adelaida Kolaj,
Siraj K. Zahr,
Beatrix S. Wang,
Taylor Krawec,
Hilal Kazan,
Guang Yang,
David R. Kaplan,
Freda D. Miller

Affiliations

Adelaida Kolaj: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5G 1A8, Canada
Siraj K. Zahr: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G1L7, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON M5G 1A8, Canada
Beatrix S. Wang: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G1L7, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON M5G 1A8, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Taylor Krawec: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Hilal Kazan: Department of Computer Engineering, Antalya Bilim University, Antalya, Turkey
Guang Yang: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada; Department of Biochemistry and Cell Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB T2N 1N4, Canada
David R. Kaplan: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1A8, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON M5G 1A8, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Freda D. Miller: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5G 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1A8, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON M5G 1A8, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Corresponding author

Journal volume & issue: Vol. 42, no. 3
p. 112242

Abstract

Read online

Summary: Here, we ask how developing precursors maintain the balance between cell genesis for tissue growth and establishment of adult stem cell pools, focusing on postnatal forebrain neural precursor cells (NPCs). We show that these NPCs are transcriptionally primed to differentiate and that the primed mRNAs are associated with the translational repressor 4E-T. 4E-T also broadly associates with other NPC mRNAs encoding transcriptional regulators, and these are preferentially depleted from ribosomes, consistent with repression. By contrast, a second translational regulator, Cpeb4, associates with diverse target mRNAs that are largely ribosome associated. The 4E-T-dependent mRNA association is functionally important because 4E-T knockdown or conditional knockout derepresses proneurogenic mRNA translation and perturbs maintenance versus differentiation of early postnatal NPCs in culture and in vivo. Thus, early postnatal NPCs are primed to differentiate, and 4E-T regulates the balance between cell genesis and stem cell expansion by sequestering and repressing mRNAs encoding transcriptional regulators.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords