title: A multifunctional protein EWS regulates the expression of Drosha and microRNAs.
abstract: EWS (Ewing's Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (Col4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of Col4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of Col4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of Col4a1 and CTGF via a Drosha-miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis.
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea.
authors.forename: K Y
authors.initials: KY
authors.lastname: Kim
authors.forename: Y J
authors.initials: YJ
authors.lastname: Hwang
authors.forename: M-K
authors.initials: MK
authors.lastname: Jung
authors.forename: J
authors.initials: J
authors.lastname: Choe
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: C-J
authors.initials: CJ
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Ahn
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: N W
authors.initials: NW
authors.lastname: Kowall
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.forename: J-I
authors.initials: JI
authors.lastname: Kim
authors.forename: S B
authors.initials: SB
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Ryu
mesh_terms: D000818:Animals; D002460:Cell Line; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D034802:RNA-Binding Protein EWS / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C526318:CCN2 protein, mouse; D024141:Collagen Type IV; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D034741:RNA, Small Interfering; D034802:RNA-Binding Protein EWS; D055513:Connective Tissue Growth Factor; C513400:Drosha protein, mouse; D043244:Ribonuclease III