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

  1. Camilla Nehammer
  2. Patrick Ejlerskov
  3. Sandeep Gopal
  4. Ava Handley
  5. Leelee Ng
  6. Pedro Moreira
  7. Huikyong Lee
  8. Shohreh Issazadeh-Navikas
  9. David C Rubinsztein
  10. Roger Pocock  Is a corresponding author
  1. University of Copenhagen, Denmark
  2. Monash University, Australia
  3. University of Cambridge, United Kingdom

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-b (IFN-b) 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.

Data availability

RNA sequencing data have been deposited in GEO under accession code GSE128968

The following data sets were generated

Article and author information

Author details

  1. Camilla Nehammer

    Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  2. Patrick Ejlerskov

    Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  3. Sandeep Gopal

    Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Ava Handley

    Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1543-1551
  5. Leelee Ng

    Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Pedro Moreira

    Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Huikyong Lee

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Shohreh Issazadeh-Navikas

    Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  9. David C Rubinsztein

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5002-5263
  10. Roger Pocock

    Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
    For correspondence
    roger.pocock@monash.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5515-3608

Funding

National Health and Medical Research Council (GNT1137645)

  • Roger Pocock

Lundbeckfonden (R223-2016-849)

  • Shohreh Issazadeh-Navikas

Lundbeckfonden (R210-2015-3372)

  • Patrick Ejlerskov

Wellcome (095317/Z/11/Z)

  • David C Rubinsztein

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hitoshi Nakatogawa, Tokyo Institute of Technology, Japan

Publication history

  1. Received: July 4, 2019
  2. Accepted: December 3, 2019
  3. Accepted Manuscript published: December 4, 2019 (version 1)
  4. Version of Record published: December 16, 2019 (version 2)

Copyright

© 2019, Nehammer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Camilla Nehammer
  2. Patrick Ejlerskov
  3. Sandeep Gopal
  4. Ava Handley
  5. Leelee Ng
  6. Pedro Moreira
  7. Huikyong Lee
  8. Shohreh Issazadeh-Navikas
  9. David C Rubinsztein
  10. Roger Pocock
(2019)
Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy
eLife 8:e49930.
https://doi.org/10.7554/eLife.49930
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