title: MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans.
abstract: Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional 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. Here we show that in C. elegans mir-34 upregulation is necessary for developmental arrest, correct morphogenesis, and adaptation to a lower metabolic state to protect animals against stress-related damage. Either deletion or overexpression of mir-34 lead to an impaired stress response, which can largely be explained by perturbations in DAF-16/FOXO target gene expression. 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.
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.|Joslin Diabetes Center, Harvard Stem Cell Institute and Harvard Medical School Department of Genetics, Boston, Massachusetts, United States of America.
authors.forename: Meltem
authors.initials: M
authors.lastname: Isik
authors.affiliation: Joslin Diabetes Center, Harvard Stem Cell Institute and Harvard Medical School Department of Genetics, Boston, Massachusetts, United States of America.
authors.forename: T Keith
authors.initials: TK
authors.lastname: Blackwell
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.|European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Eugene
authors.initials: E
authors.lastname: Berezikov
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C000607630:MIRN34 microRNA, C elegans; D035683:MicroRNAs; C108831:daf-16 protein, C elegans