TY - JOUR TI - Sam68 promotes self-renewal and glycolytic metabolism in mouse neural progenitor cells by modulating Aldh1a3 pre-mRNA 3'-end processing AU - La Rosa, Piergiorgio AU - Bielli, Pamela AU - Compagnucci, Claudia AU - Cesari, Eleonora AU - Volpe, Elisabetta AU - Farioli Vecchioli, Stefano AU - Sette, Claudio A2 - Bronner, Marianne VL - 5 PY - 2016 DA - 2016/11/15 SP - e20750 C1 - eLife 2016;5:e20750 DO - 10.7554/eLife.20750 UR - https://doi.org/10.7554/eLife.20750 AB - 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. KW - Sam68 KW - pre-mRNA processing KW - alternative splicing KW - ALDH1A3 KW - neural progenitor cells KW - glycolytic metabolism JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -