Nuclear retention of MBP mRNAs in the quaking viable mice.
Quaking viable (qk(v)) mice fail to properly compact myelin in their central nervous systems. Although the defect in the qk(v) mice involves a mutation affecting the expression of the alternatively spliced qk gene products, their roles in myelination are unknown. We show that the QKI RNA binding proteins regulate the nuclear export of MBP mRNAs. Disruption of the QKI nucleocytoplasmic equilibrium in oligodendrocytes results in nuclear and perikaryal retention of the MBP mRNAs and lack of export to cytoplasmic processes, as it occurs in qk(v) mice. MBP mRNA export defect leads to a reduction in the MBP levels and their improper cellular targeting to the periphery. Our findings suggest that QKI participates in myelination by regulating the mRNA export of key protein components.
Larocque
Daniel
D
Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, Québec, Canada.
Pilotte
Julie
J
Chen
Taiping
T
Cloutier
Frank
F
Massie
Bernard
B
Pedraza
Liliana
L
Couture
Réjean
R
Lasko
Paul
P
Almazan
Guillermina
G
Richard
Stéphane
S
D020413:3' Untranslated Regions / Q000378:metabolism; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D006801:Humans; D051379:Mice; D008821:Mice, Quaking; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology; D017354:Point Mutation; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D004676:Myelin Basic Protein; D020033:Protein Isoforms; C490832:QKI protein, human; C098217:Qk protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins