Document Detail

The QKI-5 and QKI-6 RNA binding proteins regulate the expression of microRNA 7 in glial cells.
MedLine Citation:
PMID:  23319046     Owner:  NLM     Status:  MEDLINE    
The quaking (qkI) gene encodes 3 major alternatively spliced isoforms that contain unique sequences at their C termini dictating their cellular localization. QKI-5 is predominantly nuclear, whereas QKI-6 is distributed throughout the cell and QKI-7 is cytoplasmic. The QKI isoforms are sequence-specific RNA binding proteins expressed mainly in glial cells modulating RNA splicing, export, and stability. Herein, we identify a new role for the QKI proteins in the regulation of microRNA (miRNA) processing. We observed that small interfering RNA (siRNA)-mediated QKI depletion of U343 glioblastoma cells leads to a robust increase in miR-7 expression. The processing from primary to mature miR-7 was inhibited in the presence QKI-5 and QKI-6 but not QKI-7, suggesting that the nuclear localization plays an important role in the regulation of miR-7 expression. The primary miR-7-1 was bound by the QKI isoforms in a QKI response element (QRE)-specific manner. We observed that the pri-miR-7-1 RNA was tightly bound to Drosha in the presence of the QKI isoforms, and this association was not observed in siRNA-mediated QKI or Drosha-depleted U343 glioblastoma cells. Moreover, the presence of the QKI isoforms led to an increase presence of pri-miR-7 in nuclear foci, suggesting that pri-miR-7-1 is retained in the nucleus by the QKI isoforms. miR-7 is known to target the epidermal growth factor (EGF) receptor (EGFR) 3' untranslated region (3'-UTR), and indeed, QKI-deficient U343 cells had reduced EGFR expression and decreased ERK activation in response to EGF. Elevated levels of miR-7 are associated with cell cycle arrest, and it was observed that QKI-deficient U343 that harbor elevated levels of miR-7 exhibited defects in cell proliferation that were partially rescued by the addition of a miR-7 inhibitor. These findings suggest that the QKI isoforms regulate glial cell function and proliferation by regulating the processing of certain miRNAs.
Yunling Wang; Gillian Vogel; Zhenbao Yu; Stéphane Richard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-14
Journal Detail:
Title:  Molecular and cellular biology     Volume:  33     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-22     Completed Date:  2013-07-05     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1233-43     Citation Subset:  IM    
Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research and Departments of Oncology and Medicine, McGill University, Montreal, Quebec, Canada.
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MeSH Terms
Cell Growth Processes / physiology
Cell Line
Cell Nucleus / genetics,  metabolism
Epidermal Growth Factor / genetics,  metabolism
HEK293 Cells
MAP Kinase Signaling System / genetics
MicroRNAs / biosynthesis,  genetics*
Neuroglia / metabolism,  physiology*
Protein Binding
Protein Isoforms
RNA-Binding Proteins / genetics*,  metabolism*
Receptor, Epidermal Growth Factor / genetics,  metabolism
Ribonuclease III / genetics,  metabolism
Reg. No./Substance:
0/MIRN7 microRNA, human; 0/MicroRNAs; 0/Protein Isoforms; 0/QKI protein, human; 0/RNA-Binding Proteins; 62229-50-9/Epidermal Growth Factor; EC protein, human; EC, Epidermal Growth Factor; EC protein, human; EC III

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