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Publication : A multifunctional protein EWS regulates the expression of Drosha and microRNAs.

First Author  Kim KY Year  2014
Journal  Cell Death Differ Volume  21
Issue  1 Pages  136-45
PubMed ID  24185621 Mgi Jnum  J:229070
Mgi Id  MGI:5750294 Doi  10.1038/cdd.2013.144
Citation  Kim KY, et al. (2014) A multifunctional protein EWS regulates the expression of Drosha and microRNAs. Cell Death Differ 21(1):136-45
abstractText  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.
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