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

• Published in: Cellular and molecular life sciences : CMLS Vol. 74; no. 19; pp. 3613 - 3630
• Main Authors: Kwok, Hoi-Hin, Poon, Po-Ying, Mak, Kylie Hin-Man, Zhang, Lin-Yao, Liu, Pei, Zhang, Huoming, Mak, Nai-Ki, Yue, Patrick Ying-Kit, Wong, Ricky Ngok-Shun
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2017; Springer Nature B.V
• Subjects: Active Transport, Cell Nucleus; agonists; AKT protein; Base Sequence; Binding; Binding Sites; Biochemistry; biogenesis; Biomedical and Life Sciences; Biomedicine; Biosynthesis; Cell Biology; Cells; consensus sequence; Conserved sequence; Dexamethasone; DNA Helicases - chemistry; DNA Helicases - metabolism; Endothelial Cells; Estrogens; Gene expression; Gene Expression Regulation - drug effects; Ginsenosides; glucocorticoid receptors; Glucocorticoids; GTPase-activating protein; GTPase-activating proteins; Guanosine triphosphatases; Homology; hormonal regulation; Human Umbilical Vein Endothelial Cells; Humans; Life Sciences; Maturation; mice; microRNA; MicroRNAs; MicroRNAs - chemistry; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neurons; non-coding RNA; Nuclear transport; oncogenes; Original; Original Article; Phosphorylation; Poly-ADP-Ribose Binding Proteins - chemistry; Poly-ADP-Ribose Binding Proteins - metabolism; Protein Binding - drug effects; Proteins; Proteomics; Proto-Oncogene Proteins c-akt - metabolism; Receptors, Glucocorticoid - agonists; Receptors, Glucocorticoid - metabolism; Ribonucleic acid; RNA; RNA Helicases - chemistry; RNA Helicases - metabolism; RNA Recognition Motif Proteins - chemistry; RNA Recognition Motif Proteins - metabolism; RNA-binding protein; RNA-binding proteins; Thymoma; Translocation; Vascular system; microRNA; GR; miRNA biogenesis; Glucocorticoid; G3BP1
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-017-2540-y

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.