Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy.
Camilla NehammerPatrick EjlerskovSandeep GopalAva HandleyLeelee NgPedro MoreiraHuikyong LeeShohreh Issazadeh-NavikasDavid C RubinszteinRoger PocockPublished in: eLife (2019)
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.
Keyphrases
- cell proliferation
- cell death
- endoplasmic reticulum stress
- long non coding rna
- signaling pathway
- induced apoptosis
- oxidative stress
- long noncoding rna
- poor prognosis
- dendritic cells
- cell cycle arrest
- binding protein
- protein protein
- transcription factor
- amino acid
- immune response
- pi k akt
- diabetic rats
- mouse model
- high glucose
- drug induced