Projects per year
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 language | English |
---|---|
Article number | e49930 |
Number of pages | 24 |
Journal | eLife |
Volume | 8 |
DOIs | |
Publication status | Published - 4 Dec 2019 |
Keywords
- autophagy
- biochemistry
- C. elegans
- chemical biology
- genetics
- genomics
- human cells
- mammalian cells
- microRNA
- protein aggregation
Projects
- 2 Finished
-
CALCIUM-MEDIATED REGULATION OF STEM CELL DEVELOPMENT
Gopal, S.
Australian Research Council (ARC)
1/01/19 → 31/12/21
Project: Research
-
Role of Transient Ca2+ in Transcriptional Wiring of Stem Cells
Gopal, S., Pocock, R. & Griesbeck, O.
1/01/19 → 31/03/22
Project: Research
Equipment
-
Bioinformatics Platform
David Powell (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
-
Micromon
Scott Coutts (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility