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Aging (Albany NY). 2016 Sep 12;8(9):1979-2005. doi: 10.18632/aging.101029.

An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in C. elegans.

Author information

1
The Laboratory of Ageing, Centenary Institute, Camperdown, NSW 2050, Australia.
2
Sydney Medical School, The University of Sydney, Camperdown, NSW 2050, Australia.
3
Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA.
4
Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.

Abstract

Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C. elegans promotes an adaptive response to chronic - a mild and long-term - oxidative stress exposure. The pathway involved appears to be unique since the canonical stress-responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in xenobiotic metabolism and pathogen defense responses are up-regulated by the loss of mir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis.

KEYWORDS:

C. elegans; adaptive response; aging; microRNA; oxidative stress

PMID:
27623524
PMCID:
PMC5076448
DOI:
10.18632/aging.101029
[Indexed for MEDLINE]
Free PMC Article

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