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

Handle URI:
http://hdl.handle.net/10754/625021
Title:
Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells
Authors:
Kwok, Hoi-Hin; Poon, Po-Ying; Mak, Kylie Hin-Man; Zhang, Lin-Yao; Liu, Pei; Zhang, Huoming ( 0000-0001-5416-0358 ) ; Mak, Nai-Ki; Yue, Patrick Ying-Kit; Wong, Ricky Ngok-Shun
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.
KAUST Department:
Biosciences Core Lab
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.
Publisher:
Springer Nature
Journal:
Cellular and Molecular Life Sciences
Issue Date:
18-May-2017
DOI:
10.1007/s00018-017-2540-y
Type:
Article
ISSN:
1420-682X; 1420-9071
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.
Additional Links:
http://link.springer.com/article/10.1007/s00018-017-2540-y
Appears in Collections:
Articles; Biosciences Core Lab

Full metadata record

DC FieldValue Language
dc.contributor.authorKwok, Hoi-Hinen
dc.contributor.authorPoon, Po-Yingen
dc.contributor.authorMak, Kylie Hin-Manen
dc.contributor.authorZhang, Lin-Yaoen
dc.contributor.authorLiu, Peien
dc.contributor.authorZhang, Huomingen
dc.contributor.authorMak, Nai-Kien
dc.contributor.authorYue, Patrick Ying-Kiten
dc.contributor.authorWong, Ricky Ngok-Shunen
dc.date.accessioned2017-06-14T12:17:34Z-
dc.date.available2017-06-14T12:17:34Z-
dc.date.issued2017-05-18en
dc.identifier.citationKwok 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.en
dc.identifier.issn1420-682Xen
dc.identifier.issn1420-9071en
dc.identifier.doi10.1007/s00018-017-2540-yen
dc.identifier.urihttp://hdl.handle.net/10754/625021-
dc.description.abstractMicroRNAs (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.en
dc.description.sponsorshipWe 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.en
dc.publisherSpringer Natureen
dc.relation.urlhttp://link.springer.com/article/10.1007/s00018-017-2540-yen
dc.subjectGlucocorticoiden
dc.subjectGRen
dc.subjectMicroRNAen
dc.subjectMirna Biogenesisen
dc.subjectG3bp1en
dc.titleRole of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cellsen
dc.typeArticleen
dc.contributor.departmentBiosciences Core Laben
dc.identifier.journalCellular and Molecular Life Sciencesen
dc.contributor.institutionDr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.en
dc.contributor.institutionDepartment of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.en
dc.contributor.institutionDr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. rnswong@hkbu.edu.hk.en
kaust.authorZhang, Huomingen
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