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

Abstract
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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-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

1. Archer SK
2. Nehammer C
3. Ejlerskov P
4. Gopal S
5. Handley A
6. Ng L
7. Moreira P
8. Rubinsztein DC
9. Pocock R
(2019) Transcriptome analysis of mir-1-deficient and ins-1-deficient Caenorhabditis elegans
NCBI Gene Expression Omnibus, GSE128968.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE128968

Article and author information

Author details

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.
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.
Sandeep Gopal

Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Ava Handley

Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1543-1551
Leelee Ng

Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Pedro Moreira

Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Huikyong Lee

Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
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.
David C Rubinsztein

Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5002-5263
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.

"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.

Copyright

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.