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Status |
Public on Dec 02, 2016 |
Title |
MicroRNA mir-34 provides robustness to environmental stress response in C. elegans |
Organism |
Caenorhabditis elegans |
Experiment type |
Expression profiling by array
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Summary |
Diverse stresses and aging result in changes in expression levels of microRNAs, suggesting a role for these posttrancriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following stress in human cells. However, the biological significance of this response was unclear, because wildtype and miR-34 family knockouts tested under a variety of stress conditions showed no difference in cell survival in vitro or in vivo. Here, we addressed this question in C. elegans by analyzing the effect of different stress conditions on phenotype, transcriptome and mir-34 expression in animals deficient in or overexpressing mir-34. We showed that mir-34 upregulation is necessary for developmental arrest, correct morphogenesis, and adaptation to a lower metabolic state to protect animals against stress-related damages. Either deletion or overexpression of mir-34 lead to impaired stress response, which can largely be explained by perturbations in a DAF-16/FOXO target genes. We demonstrate that mir-34 expression is regulated by the insulin signaling pathway via a negative feedback loop between miR-34 and DAF-16/FOXO. We propose that mir-34 provides robustness to stress response programs by controlling noise in the DAF-16/FOXO-regulated gene network.
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Overall design |
Gene expression levels at different temperatures and in different genetic backgrounds (wild-type, mir-34 deletion or overxepression, daf2) in adult animals or in daures were measured. Three replicates were performed for most conditions.
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Contributor(s) |
Isik M, Berezikov E |
Citation(s) |
27905558 |
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Submission date |
Dec 30, 2015 |
Last update date |
Dec 04, 2016 |
Contact name |
Eugene Berezikov |
E-mail(s) |
e.berezikov@umcg.nl
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Phone |
+31 50 361 73 00
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Organization name |
University Medical Center Groningen
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Department |
European Research Institute for the Biology of Ageing
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Street address |
Antonius Deusinglaan 1
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City |
Groningen |
ZIP/Postal code |
9713AV |
Country |
Netherlands |
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Platforms (1) |
GPL10094 |
Agilent-020186 C. elegans (V2) Gene Expression Microarray (Feature Number version) |
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Samples (30)
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Relations |
BioProject |
PRJNA307238 |