An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress inC. elegans.
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 nematodeC. eleganspromotes 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 formir-60loss 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 ofmir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor genezip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that themir-60loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis.
The Laboratory of Ageing, Centenary Institute, Camperdown, NSW 2050, Australia.|Sydney Medical School, The University of Sydney, Camperdown, NSW 2050, Australia.
Masaomi
M
Kato
The Laboratory of Ageing, Centenary Institute, Camperdown, NSW 2050, Australia.|Sydney Medical School, The University of Sydney, Camperdown, NSW 2050, Australia.
Mohammed Abul
MA
Kashem
Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA.|Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.
Chao
C
Cheng
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D015854:Up-Regulation
D029742:Caenorhabditis elegans Proteins; D027682:Cation Transport Proteins; D035683:MicroRNAs
C. elegans; adaptive response; aging; microRNA; oxidative stress