MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans

• Published in: Scientific reports Vol. 6; no. 1; p. 36766
• Main Authors: Isik, Meltem, Blackwell, T. Keith, Berezikov, Eugene
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2016; Nature Publishing Group
• Subjects: 14/63; 38; 38/61; 631/208/135; 631/208/200; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell cycle; Cell death; Clonal deletion; Environmental stress; Feedback; Forkhead protein; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene expression; Gene Expression Regulation; Humanities and Social Sciences; Insulin; Longevity; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Morphogenesis; multidisciplinary; Noise control; Post-transcription; Science; Signal transduction; Stress response; Stress, Physiological
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep36766

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.