A multifunctional protein EWS regulates the expression of Drosha and microRNAs

Title
A multifunctional protein EWS regulates the expression of Drosha and microRNAs
Authors
김기윤황유진정민경최준호김연하김선이채진안홍렬이정희Neil W. Kowall김윤기김종일Lee Sean Bong류훈
Keywords
EWS; Drosha; miRNA; CTGF; dermal development
Issue Date
2014-01
Publisher
Cell death and differentiation
Citation
VOL 21, NO 1, 136-145
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.
URI
http://pubs.kist.re.kr/handle/201004/46886
ISSN
13509047
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KIST Publication > Article
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