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

Claudio Sette, Eleonora Cesari, Piergiorgio La Rosa, Pamela Bielli, Claudia Compagnucci, Elisabetta Volpe, Stefano Farioli Vecchioli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

32 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaeLife
Volume5
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • ALDH1A3
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Biochemistry, Genetics and Molecular Biology (all)
  • Cell Differentiation
  • Cell Proliferation
  • Gene Knockout Techniques
  • Glycolysis
  • Immunology and Microbiology (all)
  • Mice
  • Neocortex
  • Neural Stem Cells
  • Neuroscience (all)
  • Protein Binding
  • RNA Precursors
  • RNA-Binding Proteins
  • Retinal Dehydrogenase
  • Sam68
  • Stem Cells
  • Transcription, Genetic
  • alternative splicing
  • cell biology
  • glycolytic metabolism
  • mouse
  • neural progenitor cells
  • neuroscience
  • pre-mRNA processing

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