Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

Abstract
Data availability
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Abstract

The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by important known stem cell-extrinsic signals. However, the cell-intrinsic mechanisms that control the distinctive proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, and heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.

Data availability

The presented RNA sequencing data has been deposited with Gene Expression Omnibus (GEO), with accession number GSE140704.

The following data sets were generated

(2019) Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability
NCBI Gene Expression Omnibus, GSE140704.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE140704

The following previously published data sets were used

(2015) Drosophila Imp iCLIP identifies an RNA assemblage co-ordinating F-actin formation
NCBI Gene Expression Omnibus, GSE62997.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62997

Article and author information

Author details

Tamsin J Samuels

Department of Biochemistry, University of Oxford, Oxford, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Aino I Järvelin

Department of Biochemistry, University of Oxford, Oxford, United Kingdom

Competing interests
The authors declare that no competing interests exist.
David Ish-Horowicz

MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Ilan Davis

Department of Biochemistry, University of Oxford, Oxford, United Kingdom

For correspondence
ilan.davis@bioch.ox.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5385-3053

Funding

Wellcome (105363/Z/14/Z)

Tamsin J Samuels

Wellcome (096144/Z/17/Z)

Aino I Järvelin
Ilan Davis

Wellcome (209412/Z/17/Z)

Tamsin J Samuels
Aino I Järvelin
Ilan Davis

University College London

David Ish-Horowicz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.