Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy
Year: 2019
Type: article
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.
Source: eLife
DOI: 10.7554/elife.49930
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: University of Minnesota, Wellcome Trust, Veski, Alzheimer's Society, National Institute for Health and Care Research, Department of Health and Social Care, Lundbeckfonden, Danmarks Frie Forskningsfond, H. Lundbeck A/S, UK Dementia Research Institute, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, NIHR Cambridge Biomedical Research Centre
OpenAlex ID: W2992390719