| The QKI-5 and QKI-6 RNA binding proteins regulate the expression of miR-7 in glial cells. | |
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MedLine Citation:
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PMID: 23319046 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The quaking (qkI) gene encodes 3 major alternatively spliced isoforms that contain unique sequences at their C-terminus 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 miRNA processing. We observe that 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' -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 was 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. |
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Authors:
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Yunling Wang; Gillian Vogel; Zhenbao Yu; Stéphane Richard |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-14 |
Journal Detail:
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Title: Molecular and cellular biology Volume: - ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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, Canada H3T 1E2. |
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