Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy
Authors
Nehammer, Camilla
Ejlerskov, Patrick
Gopal, Sandeep
Ng, Leelee
Moreira, Pedro
Lee, Huikyong
Issazadeh-Navikas, Shohreh
Publication Date
2019-12-04Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Nehammer, C., Ejlerskov, P., Gopal, S., Handley, A., Ng, L., Moreira, P., Lee, H., et al. (2019). Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy. https://doi.org/10.7554/elife.49930
Abstract
Appropriate regulation of autophagy is crucial for clearing toxic proteins from cells. Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous Tre-2/Bub2/CDC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. Loss of miR-1 causes TBC-7/TBC1D15 overexpression, leading to a block on autophagy. Further, we found that the cytokine interferon-β (IFN-β) can induce miR-1 expression in mammalian cells, reducing TBC1D15 levels, and safeguarding against proteotoxic challenges. Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders.
Keywords
Research Article, Biochemistry and Chemical Biology, Genetics and Genomics, microRNA, autophagy, protein aggregation, mammalian cells, human cells, C. elegans
Sponsorship
National Health and Medical Research Council (GNT1137645)
Lundbeckfonden (R223-2016-849)
Lundbeckfonden (R210-2015-3372)
Wellcome (095317/Z/11/Z)
Det Frie Forskningsråd (DFF-6110-00461)
Veski (VIF23)
Det Frie Forskningsråd (DFF-6110–00658)
Identifiers
49930
External DOI: https://doi.org/10.7554/elife.49930
This record's URL: https://www.repository.cam.ac.uk/handle/1810/300008
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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