The QKI-6 RNA Binding Protein Regulates Actin-Interacting protein-1 mRNA Stability During Oligodendrocyte Differentiation

Mol Biol Cell. 2010 Sep 1;21(17):3029-40. doi: 10.1091/mbc.E10-04-0305. Epub 2010 Jul 14.

Abstract

The quaking viable (qk(v)) mice represent an animal model of dysmyelination. The absence of expression of the QKI-6 and QKI-7 cytoplasmic isoforms in oligodendrocytes (OLs) during CNS myelination causes the qk(v) mouse phenotype. The QKI RNA-binding proteins are known to regulate RNA metabolism of cell cycle proteins and myelin components in OLs; however, little is known of their role in reorganizing the cytoskeleton or process outgrowth during OL maturation and differentiation. Here, we identify the actin-interacting protein (AIP)-1 mRNA as a target of QKI-6 by using two-dimensional differential gel electrophoresis. The AIP-1 mRNA contains a consensus QKI response element within its 3'-untranslated region that, when bound by QKI-6, decreases the half-life of the AIP-1 mRNA. Although the expression of QKI-6 is known to increase during OL differentiation and CNS myelination, we show that this increase is paralleled with a corresponding decrease in AIP-1 expression in rat brains. Furthermore, qk(v)/qk(v) mice that lack QKI-6 and QKI-7 within its OLs had an increased level of AIP-1 in OLs. Moreover, primary rat OL precursors harboring an AIP-1 small interfering RNA display defects in OL process outgrowth. Our findings suggest that the QKI RNA-binding proteins regulate OL differentiation by modulating the expression of AIP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Actin Cytoskeleton / metabolism
  • Actin Depolymerizing Factors / metabolism
  • Animals
  • Cell Differentiation*
  • Cell Line, Tumor
  • Cell Surface Extensions / metabolism
  • Central Nervous System / metabolism
  • Gene Expression Regulation
  • Humans
  • Mice
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Myelin Sheath / metabolism
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism*
  • Protein Binding
  • Protein Transport
  • RNA Stability*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Two-Dimensional Difference Gel Electrophoresis

Substances

  • 3' Untranslated Regions
  • Actin Depolymerizing Factors
  • Microfilament Proteins
  • QKI protein, human
  • Qk protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • actin interacting protein 1