Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy
- University of Copenhagen, Denmark
- Monash University, Australia
- University of Cambridge, United Kingdom
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-b (IFN-b) 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.
Data availability
RNA sequencing data have been deposited in GEO under accession code GSE128968
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Transcriptome analysis of mir-1-deficient and ins-1-deficient Caenorhabditis elegansNCBI Gene Expression Omnibus, GSE128968.
Article and author information
Author details
David C Rubinsztein
Funding
National Health and Medical Research Council (GNT1137645)
- Roger Pocock
Lundbeckfonden (R223-2016-849)
- Shohreh Issazadeh-Navikas
Lundbeckfonden (R210-2015-3372)
- Patrick Ejlerskov
Wellcome (095317/Z/11/Z)
- David C Rubinsztein
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hitoshi Nakatogawa, Tokyo Institute of Technology, Japan
Publication history
- Received: July 4, 2019
- Accepted: December 3, 2019
- Accepted Manuscript published: December 4, 2019 (version 1)
- Version of Record published: December 16, 2019 (version 2)
Copyright
© 2019, Nehammer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy
eLife 8:e49930.
https://doi.org/10.7554/eLife.49930
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