A role for the ELAV RNA-binding proteins in neural stem cells: Stabilization of Msi1 mRNA

Antonia Ratti, Claudia Fallini, Lidia Cova, Roberto Fantozzi, Cinzia Calzarossa, Eleonora Zennaro, Alessia Pascale, Alessandro Quattrone, Vincenzo Silani

Research output: Contribution to journalArticle

Abstract

Post-transcriptional regulation exerted by neural-specific RNA-binding protein plays a pivotal role in the development and maintenance of the nervous system. Neural ELAV proteins are key inducers of neuronal differentiation through the stabilization and/or translational enhancement of target transcripts bearing the AU-rich elements (AREs), whereas Musashi-1 maintains the stem cell proliferation state by acting as a translational repressor. Since the gene encoding Musashi-1 (Msi1) contains a conserved ARE in its 3′ untranslated region, we focused on the possibility of a mechanistic relationship between ELAV proteins and Musashi-1 in cell fate commitment. Colocalization of neural ELAV proteins with Musashi-1 clearly shows that ELAV proteins are expressed at early stages of neural commitment, whereas interaction studies demonstrate that neural ELAV proteins exert an ARE-dependent binding activity on the Msi1 mRNA. This binding activity has functional effects, since the ELAV protein family member HuD is able to stabilize the Msi1 ARE-containing mRNA in a sequence-dependent way in a deadenylation/ degradation assay. Furthermore activation of the neural ELAV proteins by phorbol esters in human SH-SY5Y cells is associated with an increase of Musashi-1 protein content in the cytoskeleton. We propose that ELAV RNA-binding proteins exert an important posttranscriptional control on Musashi-1 expression in the transition from proliferation to neural differentiation of stem/progenitor cells.

Original languageEnglish
Pages (from-to)1442-1452
Number of pages11
JournalJournal of Cell Science
Volume119
Issue number7
DOIs
Publication statusPublished - Apr 1 2006

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Keywords

  • ELAV
  • Musashi-1
  • Neurogenesis
  • RNA-binding protein
  • Stem cell

ASJC Scopus subject areas

  • Cell Biology

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