Format

Send to

Choose Destination
Elife. 2016 Nov 15;5. pii: e20750. doi: 10.7554/eLife.20750.

Sam68 promotes self-renewal and glycolytic metabolism in mouse neural progenitor cells by modulating Aldh1a3 pre-mRNA 3'-end processing.

Author information

1
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
2
Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy.
3
Laboratory of Neuroimmunology, Fondazione Santa Lucia, Rome, Italy.
4
Institute of Cell Biology and Neurobiology CNR, Rome, Italy.

Abstract

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 (Khdrbs1) is strongly expressed in neurogenic areas of the neocortex and supports the self-renewing potential of mouse NPCs. Knockout of Khdrbs1 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, favoring expression of a functional enzyme. The lower ALDH1A3 expression and activity in Khdrbs1-/- 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.

KEYWORDS:

ALDH1A3; Sam68; alternative splicing; cell biology; glycolytic metabolism; mouse; neural progenitor cells; neuroscience; pre-mRNA processing

PMID:
27845622
PMCID:
PMC5122457
DOI:
10.7554/eLife.20750
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center