Kim, Yunha Kang, Young-Sook Lee, Na-Young Kim, Ki Yoon Hwang, Yu Jin Kim, Hyun-Wook Rhyu, Im Joo Her, Song Jung, Min-Kyung Kim, Sun Lee, Chai-Jin Ko, Seyoon Kowall, Neil W. Lee, Sean Bong Lee, Junghee Ryu, Hoon 2024-01-20T07:03:53Z 2024-01-20T07:03:53Z 2021-09-05 2015-05 1554-8627 https://pubs.kist.re.kr/handle/201004/125498 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. English TAYLOR & FRANCIS INC SARCOMA GENE EWS PHOSPHATIDYLINOSITOL 3-KINASE MULTIFUNCTIONAL PROTEIN MOLECULAR-MECHANISMS SELF-DIGESTION EWINGS-SARCOMA HOPS COMPLEX SYNTAXIN 17 CELL-DEATH MICRORNAS Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency Article 10.1080/15548627.2015.1035503 1 AUTOPHAGY, v.11, no.5, pp.796 - 811 AUTOPHAGY 11 5 796 811 scie scopus 000355323800007 2-s2.0-84943739752 Cell Biology Cell Biology Article SARCOMA GENE EWS PHOSPHATIDYLINOSITOL 3-KINASE MULTIFUNCTIONAL PROTEIN MOLECULAR-MECHANISMS SELF-DIGESTION EWINGS-SARCOMA HOPS COMPLEX SYNTAXIN 17 CELL-DEATH MICRORNAS autophagy EWSR1 Mir125a Mir351 UVRAG