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

Title
Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency
Authors
김연하강영숙이나영김기윤황유진김현욱류임주허송Jung, Min-Kyung김선이채진고세윤Neil W. Kowall이선봉이정희류훈
Keywords
autophagy; EWSR1; Mir125a; Mir351; UVRAG
Issue Date
2015-05
Publisher
Autophagy
Citation
VOL 11, NO 5, 796-811
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.
URI
http://pubs.kist.re.kr/handle/201004/51292
ISSN
15548627
Appears in Collections:
KIST Publication > Article
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