title: The QKI-6 RNA binding protein regulates actin-interacting protein-1 mRNA stability during oligodendrocyte differentiation.
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.
authors.affiliation: Terry Fox Molecular Oncology Group, Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research and Departments of Oncology and Medicine, McGill University, Montréal, Québec H3T1E2, Canada.
authors.forename: Evgueni
authors.initials: E
authors.lastname: Doukhanine
authors.forename: Christina
authors.initials: C
authors.lastname: Gavino
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Haines
authors.forename: Guillermina
authors.initials: G
authors.lastname: Almazan
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D008841:Actin Cytoskeleton / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D020413:3' Untranslated Regions; D051339:Actin Depolymerizing Factors; D008840:Microfilament Proteins; C490832:QKI protein, human; C098217:Qk protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C115237:actin interacting protein 1