Interferon-[beta]-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

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...

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Bibliographic Details
Published in:eLife 2019-12, Vol.8
Main Authors: Nehammer, Camilla, Ejlerskov, Patrick, Gopal, Sandeep, Handley, Ava, Ng, Leelee, Moreira, Pedro, Lee, Huikyong, Issazadeh-Navikas, Shohreh, Rubinsztein, David C, Pocock, Roger
Format: Article
Language:English
Subjects:
Biological response modifiers
Caenorhabditis elegans
Cells (Biology)
Cytokines
Interferon
MicroRNA
Proteins
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Summary: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-[beta] (IFN-[beta]) 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.49930