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

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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.

Original languageEnglish
Article numbere49930
Number of pages24
JournaleLife
Volume8
DOIs
Publication statusPublished - 4 Dec 2019

Keywords

  • autophagy
  • biochemistry
  • C. elegans
  • chemical biology
  • genetics
  • genomics
  • human cells
  • mammalian cells
  • microRNA
  • protein aggregation

Cite this

Nehammer, C., Ejlerskov, P., Gopal, S., Handley, A., Ng, L., Moreira, P., Lee, H., Issazadeh-Navikas, S., Rubinsztein, D. C., & Pocock, R. (2019). Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy. eLife, 8, [e49930]. https://doi.org/10.7554/eLife.49930