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Modulation of autophagy by miRNAs
Modulation of autophagy by miRNAs
BMB Reports. 2015. Jul, 48(7): 371-372
Copyright © 2015, Korean Society for Biochemistry and Molecular Biology
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • Received : June 20, 2015
  • Published : July 31, 2015
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About the Authors
Yunha Kim
Center for Neuromedicine, Korea Institute of Science and Technology, Seoul 136-791, Korea
Junghee Lee
Boston University Alzheimer’s Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA
Hoon Ryu
Boston University Alzheimer’s Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA
hoonryu@bu.edu

Abstract
MicroRNAs (miRNAs) can regulate the expression of genes that are involved in multiple cellular pathways. However, their targets and mechanism of action associated with the autophagy pathway are not fully investigated yet. EWSR1 (EWS RNA-Binding Protein 1/Ewing Sarcoma Break Point Region 1) gene encodes a RNA/DNA binding protein that is ubiquitously expressed and plays roles in numerous cellular processes. Recently, our group has shown that EWSR1 deficiency leads to developmental failure and accelerated senescence via processing of miRNAs, but its role in the regulation of autophagy remains elusive. In this context, we further investigated and found that EWSR1 deficiency triggers the activation of the DROSHA-mediated microprocessor complex and increases the levels of miR125a and miR351 , which directly target Uvrag . Interestingly, the miR125a - and miR351 -targeted reduction of Uvrag led to the inhibition of autophagy in both ewsr1 knockout (KO) MEFs and ewsr1 KO mice. In summary, our study demonstrates that EWSR1 is associated with the posttranscriptional regulation of Uvrag via miRNA processing. The regulation of autophagy pathway in miRNAs- Uvrag -dependent manner provides a novel mechanism of EWSR1 deficiency-related cellular dysfunction. [BMB Reports 2015; 48(7): 371-372]
Keywords
AutophagyEWSR1miR125amiR351UVRAG
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Acknowledgements
This study was supported by NIH R01 Grant (NS067283 to H.R.) and Brain Science Flagship Grant (2E25040 to H.R.) from Korea Institute of Science and Technology.
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