title: Sam68 promotes self-renewal and glycolytic metabolism in mouse neural progenitor cells by modulatingAldh1a3pre-mRNA 3'-end processing.
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 ofKhdrbs1constricted the pool of proliferating NPCs by accelerating their cell cycle exit and differentiation into post-mitotic neurons. Sam68 function was linked to regulation ofAldh1a3pre-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 inKhdrbs1-/-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.
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.|Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: La Rosa
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.|Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Bielli
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.|Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Compagnucci
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.|Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cesari
authors.affiliation: Laboratory of Neuroimmunology, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Volpe
authors.affiliation: Institute of Cell Biology and Neurobiology CNR, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Farioli Vecchioli
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.|Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Claudio
authors.identifier: 0000-0003-2864-8266
authors.initials: C
authors.lastname: Sette
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D055786:Gene Knockout Techniques; D006019:Glycolysis; D051379:Mice; D019579:Neocortex / Q000196:embryology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D012322:RNA Precursors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000235:genetics*; D013234:Stem Cells; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513253:Khdrbs1 protein, mouse; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D050697:Retinal Dehydrogenase; C508905:retinaldehyde dehydrogenase 3, mouse
keywords: ALDH1A3; Sam68; alternative splicing; cell biology; glycolytic metabolism; mouse; neural progenitor cells; neuroscience; pre-mRNA processing