Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy
Camilla Nehammer,
Patrick Ejlerskov,
Sandeep Gopal,
Ava Handley,
Leelee Ng,
Pedro Moreira,
Huikyong Lee,
Shohreh Issazadeh-Navikas,
David C Rubinsztein,
Roger Pocock
Affiliations
Camilla Nehammer
Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia; Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Patrick Ejlerskov
Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, United Kingdom
Sandeep Gopal
Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
Leelee Ng
Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
Pedro Moreira
Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
Huikyong Lee
Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, United Kingdom
Shohreh Issazadeh-Navikas
Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, United Kingdom; UK Dementia Research Institute, University of Cambridge, Cambridge, United Kingdom
Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia; Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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.
