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    Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells

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    Type
    Article
    Authors
    Kwok, Hoi-Hin
    Poon, Po-Ying
    Mak, Kylie Hin-Man
    Zhang, Lin-Yao
    Liu, Pei-Nian cc
    Zhang, Huoming cc
    Mak, Nai-Ki
    Yue, Patrick Ying-Kit
    Wong, Ricky Ngok-Shun
    KAUST Department
    Bioscience Core Lab
    Proteomics and Protein Expression
    Date
    2017-05-18
    Online Publication Date
    2017-05-18
    Print Publication Date
    2017-10
    Permanent link to this record
    http://hdl.handle.net/10754/625021
    
    Metadata
    Show full item record
    Abstract
    MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells. RNA pulldown coupled with proteomic analysis identified GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) as one of the RNA-binding proteins mediating GR-regulated miRNA maturation. Activated GR induced phosphorylation of v-AKT Murine Thymoma Viral Oncogene Homologue (AKT) kinase, which in turn phosphorylated and promoted nuclear translocation of G3BP1. The nuclear G3BP1 bound to the G3BP1 consensus sequence located on primary miR-15b~16-2 and miR-23a~27a~24-2 to inhibit their maturation. The findings from this study have advanced our understanding of the non-genomic effects of GR in the vascular system.
    Citation
    Kwok H-H, Poon P-Y, Mak KH-M, Zhang L-Y, Liu P, et al. (2017) Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells. Cellular and Molecular Life Sciences. Available: http://dx.doi.org/10.1007/s00018-017-2540-y.
    Sponsors
    We would like to thank Ms. Hoi Ki LEE for her preliminary work on this study. This work was supported by the Dr. Gilbert Hung Ginseng Laboratory Fund.
    Publisher
    Springer Nature
    Journal
    Cellular and Molecular Life Sciences
    DOI
    10.1007/s00018-017-2540-y
    PubMed ID
    28523344
    Additional Links
    http://link.springer.com/article/10.1007/s00018-017-2540-y
    ae974a485f413a2113503eed53cd6c53
    10.1007/s00018-017-2540-y
    Scopus Count
    Collections
    Articles; Bioscience Core Lab

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