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PLoS One. 2014 Mar 20;9(3):e92552. doi: 10.1371/journal.pone.0092552. eCollection 2014.

Defects in the C. elegans acyl-CoA synthase, acs-3, and nuclear hormone receptor, nhr-25, cause sensitivity to distinct, but overlapping stresses.

Author information

1
Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America.
2
Department of Physiology, University of California San Francisco, San Francisco, California, United States of America.
3
Centre d'Immunologie de Marseille-Luminy (CIML), UM2 Aix-Marseille Université, Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France.
4
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Abstract

Metazoan transcription factors control distinct networks of genes in specific tissues, yet understanding how these networks are integrated into physiology, development, and homeostasis remains challenging. Inactivation of the nuclear hormone receptor nhr-25 ameliorates developmental and metabolic phenotypes associated with loss of function of an acyl-CoA synthetase gene, acs-3. ACS-3 activity prevents aberrantly high NHR-25 activity. Here, we investigated this relationship further by examining gene expression patterns following acs-3 and nhr-25 inactivation. Unexpectedly, we found that the acs-3 mutation or nhr-25 RNAi resulted in similar transcriptomes with enrichment in innate immunity and stress response gene expression. Mutants of either gene exhibited distinct sensitivities to pathogens and environmental stresses. Only nhr-25 was required for wild-type levels of resistance to the bacterial pathogen P. aeruginosa and only acs-3 was required for wild-type levels of resistance to osmotic stress and the oxidative stress generator, juglone. Inactivation of either acs-3 or nhr-25 compromised lifespan and resistance to the fungal pathogen D. coniospora. Double mutants exhibited more severe defects in the lifespan and P. aeruginosa assays, but were similar to the single mutants in other assays. Finally, acs-3 mutants displayed defects in their epidermal surface barrier, potentially accounting for the observed sensitivities. Together, these data indicate that inactivation of either acs-3 or nhr-25 causes stress sensitivity and increased expression of innate immunity/stress genes, most likely by different mechanisms. Elevated expression of these immune/stress genes appears to abrogate the transcriptional signatures relevant to metabolism and development.

PMID:
24651852
PMCID:
PMC3961378
DOI:
10.1371/journal.pone.0092552
[Indexed for MEDLINE]
Free PMC Article
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