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

J Cell Sci. 2006 Apr 1;119(Pt 7):1442-52. doi: 10.1242/jcs.02852.


Post-transcriptional regulation exerted by neural-specific RNA-binding proteins 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 post-transcriptional control on Musashi-1 expression in the transition from proliferation to neural differentiation of stem/progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / cytology
  • Cells, Cultured
  • ELAV Proteins / genetics*
  • ELAV Proteins / metabolism*
  • Immunohistochemistry
  • Mice
  • Mice, Inbred Strains
  • Models, Biological
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Precipitin Tests
  • RNA Stability / physiology*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Stem Cells / cytology
  • Stem Cells / metabolism*


  • ELAV Proteins
  • Msi1h protein, mouse
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins