Post-developmental microRNA expression is required for normal physiology, and regulates aging in parallel to insulin/IGF-1 signaling in C. elegans
| Autor: | Eric A. Miska, Nicolas J. Lehrbach, Julian L. Griffin, Kenneth J. Murfitt, Cecilia Castro, Cei Abreu-Goodger |
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| Rok vydání: | 2012 |
| Předmět: |
Aging
DGCR8 medicine.medical_treatment RNA Stability Longevity Molecular Sequence Data Physiology Helminth genetics Article Animals Genetically Modified microRNA medicine Animals Insulin Amino Acid Sequence Insulin-Like Growth Factor I Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Gene Genes Helminth Regulation of gene expression biology Sequence Homology Amino Acid Temperature Gene Expression Regulation Developmental biology.organism_classification Receptor Insulin Protein Structure Tertiary MicroRNAs Mutation biology.protein Signal transduction RNA Helminth Signal Transduction |
| Zdroj: | RNA (New York, N.Y.). 18(12) |
| ISSN: | 1469-9001 |
| Popis: | Regulation of gene expression by microRNAs (miRNAs) is essential for normal development, but the roles of miRNAs in the physiology of adult animals are poorly understood. We have isolated a conditional allele of DGCR8/pash-1, which allows reversible and rapid inactivation of miRNA synthesis in vivo in Caenorhabditis elegans. This is a powerful new tool that allows dissection of post-developmental miRNA functions. We demonstrate that continuous synthesis of miRNAs is dispensable for cellular viability but critical for the physiology of adult animals. Loss of miRNA synthesis in the adult reduces lifespan and results in rapid aging. The insulin/IGF-1 signaling pathway is a critical determinant of lifespan, and is modulated by miRNAs. We find that although miRNA expression is required for some mechanisms of lifespan extension, it is not essential for the longevity of animals lacking insulin/IGF-1 signaling. Further, misregulated insulin/IGF-1 signaling cannot account for the reduced lifespan caused by disruption of miRNA synthesis. We show that miRNAs act in parallel with insulin/IGF-1 signaling to regulate a shared set of downstream genes important for physiological processes that determine lifespan. We conclude that coordinated transcriptional and post-transcriptional regulation of gene expression promotes longevity. |
| Databáze: | OpenAIRE |
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