title: Transactivation of microRNA-383 by steroidogenic factor-1 promotes estradiol release from mouse ovarian granulosa cells by targeting RBMS1.
abstract: Our previous studies have shown that microRNA-383 (miR-383) is one of the most down-regulated miRNA in TGF-β1-treated mouse ovarian granulosa cells (GC). However, the roles and mechanisms of miR-383 in GC function during follicular development remain unknown. In this study, we found that miR-383 was mainly expressed in GC and oocytes of mouse ovarian follicles. Overexpression of miR-383 enhanced estradiol release from GC through targeting RNA binding motif, single stranded interacting protein 1 (RBMS1). miR-383 inhibited RBMS1 by affecting its mRNA stability, which subsequently suppressed the level of c-Myc (a downstream target of RBMS1). Forced expression of RBMS1 or c-Myc attenuated miR-383-mediated steroidogenesis-promoting effects. Knockdown of the transcription factor steroidogenic factor-1 (SF-1) significantly suppressed the expression of Sarcoglycan zeta (SGCZ) (miR-383 host gene), primary and mature miR-383 in GC, indicating that miR-383 was transcriptionally regulated by SF-1. Luciferase and chromatin immunoprecipitation assays revealed that SF-1 specifically bound to the promoter region of SGCZ and directly transactivated miR-383 in parallel with SGCZ. In addition, SF-1 was involved in regulation of miR-383- and RBMS1/c-Myc-mediated estradiol release from GC. These results suggest that miR-383 functions to promote steroidogenesis by targeting RBMS1, at least in part, through inactivation of c-Myc. SF-1 acts as a positive regulator of miR-383 processing and function in GC. Understanding of regulation of miRNA biogenesis and function in estrogen production will potentiate the usefulness of miRNA in the control of reproduction and treatment of some steroid-related disorders.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.  feisun@ustc.edu.cn.
authors.forename: Mianmian
authors.initials: M
authors.lastname: Yin
authors.forename: Mingrong
authors.initials: M
authors.lastname: Lü
authors.forename: Guidong
authors.initials: G
authors.lastname: Yao
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Jie
authors.initials: J
authors.lastname: Lian
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Liang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
mesh_terms: D000818:Animals; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D016259:Genes, myc; D006107:Granulosa Cells / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D006080:Ovarian Follicle / Q000196:embryology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D049031:Sarcoglycans / Q000096:biosynthesis / Q000235:genetics; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C577009:MIRN383 microRNA, mouse; D035683:MicroRNAs; C575008:RBMS3 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D049031:Sarcoglycans; D054339:Steroidogenic Factor 1; D015534:Trans-Activators; C515058:steroidogenic factor 1, mouse; D004958:Estradiol