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Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency

Authors
Kim, YunhaKang, Young-SookLee, Na-YoungKim, Ki YoonHwang, Yu JinKim, Hyun-WookRhyu, Im JooHer, SongJung, Min-KyungKim, SunLee, Chai-JinKo, SeyoonKowall, Neil W.Lee, Sean BongLee, JungheeRyu, Hoon
Issue Date
5월-2015
Publisher
TAYLOR & FRANCIS INC
Keywords
autophagy; EWSR1; Mir125a; Mir351; UVRAG
Citation
AUTOPHAGY, v.11, no.5, pp.796 - 811
Indexed
SCIE
SCOPUS
Journal Title
AUTOPHAGY
Volume
11
Number
5
Start Page
796
End Page
811
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/93633
DOI
10.1080/15548627.2015.1035503
ISSN
1554-8627
Abstract
The EWSR1 (EWS RNA-binding protein 1/Ewing Sarcoma Break Point Region 1) gene encodes a RNA/DNA binding protein that is ubiquitously expressed and involved in various cellular processes. EWSR1 deficiency leads to impairment of development and accelerated senescence but the mechanism is not known. Herein, we found that EWSR1 modulates the Uvrag (UV radiation resistance associated) gene at the post-transcription level. Interestingly, EWSR1 deficiency led to the activation of the DROSHA-mediated microprocessor complex and increased the level of Mir125a and Mir351, which directly target Uvrag. Moreover, the Mir125a- and Mir351-mediated reduction of Uvrag was associated with the inhibition of autophagy that was confirmed in ewsr1 knockout (KO) MEFs and ewsr1 KO mice. Taken together, our data indicate that EWSR1 is involved in the post-transcriptional regulation of Uvrag via a miRNA-dependent pathway, resulting in the deregulation of autophagy inhibition. The mechanism of Uvrag and autophagy regulation by EWSR1 provides new insights into the role of EWSR1 deficiency-related cellular dysfunction.
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