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Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

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Nehammer, Camilla 
Ejlerskov, Patrick 
Gopal, Sandeep 
Ng, Leelee 


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.



Research Article, Biochemistry and Chemical Biology, Genetics and Genomics, microRNA, autophagy, protein aggregation, mammalian cells, human cells, C. elegans

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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)