A role for the ELAV RNA-binding proteins in neural stem cells: stabilization of Msi1 mRNA.
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.
Department of Neuroscience, Dino Ferrari Centre, University of Milan-IRCCS Istituto Auxologico Italiano, Via Zucchi 18, 20095 Cusano Milanino, Italy. antonia.ratti@unimi.it
Antonia
A
Ratti
Claudia
C
Fallini
Lidia
L
Cova
Roberto
R
Fantozzi
Cinzia
C
Calzarossa
Eleonora
E
Zennaro
Alessia
A
Pascale
Alessandro
A
Quattrone
Vincenzo
V
Silani
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D051959:ELAV Proteins / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011233:Precipitin Tests; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D051959:ELAV Proteins; C104786:Msi1h protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins