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RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans
- RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans
- Seo, M[Seo, Mihwa]; Seo, K[Seo, Keunhee]; Hwang, W[Hwang, Wooseon]; Koo, HJ[Koo, Hee Jung]; Hahm, JH[Hahm, Jeong-Hoon]; Yang, JS[Yang, Jae-Seong]; Han, SK[Han, Seong Kyu]; Hwang, D[Hwang, Daehee]; Kim, S[Kim, Sanguk]; Jang, SK[Jang, Sung Key]; Lee, Y[Lee, Yoontae]; Nam, HG[Nam, Hong Gil]; Lee, SJV[Lee, Seung-Jae V.]
- DGIST Authors
- Hwang, D[Hwang, Daehee]; Nam, HG[Nam, Hong Gil]
- Issue Date
- Proceedings of the National Academy of Sciences of the United States of America, 112(31), E4246-E4255
- Article Type
- Aging; Animal; Animals; Base Sequence; C. Elegans; Caenorhabditis Elegans; Caenorhabditis Elegans Protein; Caenorhabditis Elegans Proteins; Controlled Study; DAF-16 Protein, C. Elegans; DAF-2 Protein, C. Elegans; Dead Box Protein; Enzymology; Forkhead Transcription Factor; Forkhead Transcription Factors; FOXO; Gene; Gene Expression Profiling; Gene Expression Regulation; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Gene Ontology; Gene Silencing; Genes, Helminth; Genetics; Heat Stress; Hel-1 Protein, C. Elegans; Helicase 1; Insulin; Insulin-Like Growth Factor I; Insulin Receptor; Insulin/IGF-1; Intestine; Intestines; Lifespan; Longevity; Mammalia; Messenger RNA; Metabolism; Mitochondrial Respiration; Molecular Genetics; Molecular Sequence Data; Mutation; Nerve Cell; Neurons; Non-Human; Nucleotide Sequence; Oxidative Stress; Phenotype; Physiology; Priority Journal; Progeny; Protein Binding; Pseudomonas Aeruginosa; Receptor, Insulin; Regulatory Mechanism; Reproduction; RNA Helicase; RNA Helicases; RNA Interference; RNA Sequence; RNA, Messenger; Sequence Analysis; Sequence Analysis, RNA; Signal Transduction; Somatomedin; Somatomedin 1; Somatomedin C; Transcription Factor Daf16; Transcription Factor FOXO; Transgene; Unclassified Drug; Up-Regulation; Upregulation
- The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans.
- National Academy of Sciences
- Related Researcher
Systems Biology and Medicine Lab
Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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- Department of New BiologySystems Biology and Medicine Lab1. Journal Articles
Department of New BiologyCBRG(Complex Biology Research Group)1. Journal Articles
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