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

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...

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Bibliographic Details
Published in:eLife 2019-12, Vol.8
Main Authors: Nehammer, Camilla, Ejlerskov, Patrick, Gopal, Sandeep, Handley, Ava, Ng, Leelee, Moreira, Pedro, Lee, Huikyong, Issazadeh-Navikas, Shohreh, Rubinsztein, David C, Pocock, Roger
Format: Article
Language:English
Subjects:
3' Untranslated Regions - genetics
Animals
Autophagy
Base Sequence
Biochemistry and Chemical Biology
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Experiments
Gene expression
Genetics and Genomics
Genotype & phenotype
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - metabolism
Guanosine triphosphatases
HeLa Cells
human cells
Humans
Huntingtin Protein - metabolism
Insects
Interferon-beta - metabolism
Mammalian cells
Mice
microRNA
MicroRNAs
MicroRNAs - metabolism
miRNA
Motility
Mutant Proteins - metabolism
Mutation
Nematodes
Peptides - metabolism
Phagocytosis
Protein Aggregates
protein aggregation
Protein interaction
Proteins
rab GTP-Binding Proteins - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
β-Interferon
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Description
Summary: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 re-2/ ub2/ DC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.49930