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

Yunha Kim, Young Sook Kang, Na Young Lee, Ki Yoon Kim, Yu Jin Hwang, Hyun Wook Kim, Im Joo Rhyu, Song Her, Min Kyung Jung, Sun Kim, Chai Jin Lee, Seyoon Ko, Neil W. Kowall, Sean Bong Lee, Junghee Lee, Hoon Ryu

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)796-811
Number of pages16
JournalAutophagy
Volume11
Issue number5
DOIs
Publication statusPublished - 2015 Jan 1

Keywords

  • Autophagy
  • EWSR1
  • Mir125a
  • Mir351
  • UVRAG

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Kim, Y., Kang, Y. S., Lee, N. Y., Kim, K. Y., Hwang, Y. J., Kim, H. W., Rhyu, I. J., Her, S., Jung, M. K., Kim, S., Lee, C. J., Ko, S., Kowall, N. W., Lee, S. B., Lee, J., & Ryu, H. (2015). Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency. Autophagy, 11(5), 796-811. https://doi.org/10.1080/15548627.2015.1035503