Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31799933.
- Also identified by DOI 10.7554/eLife.49930 and PMC identifier 6914338.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <u>T</u>re-2/<u>B</u>ub2/<u>C</u>DC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in <i>Caenorhabditis elegans</i> 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.
Medical subject headings
- Autophagy
- Caenorhabditis elegans
- Interferon-beta
- MicroRNAs
- Protein Aggregates