Sam68 promotes self-renewal and glycolytic metabolism in mouse neural progenitor cells by modulating Aldh1a3 pre-mRNA 3'-end processing
The balance between self-renewal and differentiation of neural progenitor cells (NPCs) dictates neurogenesis and proper brain development. We found that the RNA binding protein Sam68 is strongly expressed in neurogenic areas of the neocortex and supports the self-renewing potential of mouse NPCs. Knockout of Sam68 constricted the pool of proliferating NPCs by accelerating their cell cycle exit and differentiation into post-mitotic neurons. Sam68 function was linked to regulation of Aldh1a3 pre-mRNA 3'-end processing. Binding of Sam68 to an intronic polyadenylation site prevents its recognition and premature transcript termination, favouring expression of a functional enzyme. The lower ALDH1A3 expression and activity in Sam68-/- NPCs results in reduced glycolysis and clonogenicity, thus depleting the embryonic NPC pool and limiting cortical expansion. Our study identifies Sam68 as a key regulator of NPC self-renewal and establishes a novel link between modulation of ALDH1A3 expression and maintenance of high glycolytic metabolism in the developing cortex.
Article and author information
- Claudio Sette
Associazione Italiana Ricerca sul Cancro (IG14581)
- Claudio Sette
Muscular Dystrophy Association
- Claudio Sette
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Italian Ministry of Health. All of the animals were handled according to approved institutional animal care and use committee of the University ofRome Tor Vergata. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Rome Tor Vergata. Every effort was made to minimize suffering of mice.
- Marianne Bronner, California Institute of Technology, United States
- Received: August 17, 2016
- Accepted: November 14, 2016
- Accepted Manuscript published: November 15, 2016 (version 1)
- Version of Record published: November 24, 2016 (version 2)
© 2016, La Rosa et al.
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.
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