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

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

eLife (2019-12-05)
Camilla Nehammer, Patrick Ejlerskov, Sandeep Gopal, Ava Handley, Leelee Ng, Pedro Moreira, Huikyong Lee, Shohreh Issazadeh-Navikas, David C Rubinsztein, Roger Pocock
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phosphatase Inhibitor Cocktail 3, DMSO solution
Sigma-Aldrich
Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
Sigma-Aldrich
DAPI, dilactate, ≥98% (HPLC)
Millipore
Immobilon®-FL PVDF Membrane, 10 sheets, 20 cm x 20 cm, 0.45 µm pore size, Hydrophobic PVDF Transfer Membrane with low background fluorescence for Western blotting. Compatible with visible and infrared fluorescent probes.