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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]
Issued Date
Article Type
AgingAnimalAnimalsBase SequenceC. ElegansCaenorhabditis ElegansCaenorhabditis Elegans ProteinCaenorhabditis Elegans ProteinsControlled StudyDAF-16 Protein, C. ElegansDAF-2 Protein, C. ElegansDead Box ProteinEnzymologyForkhead Transcription FactorForkhead Transcription FactorsFOXOGeneGene Expression ProfilingGene Expression RegulationGene Expression Regulation, DevelopmentalGene Knockdown TechniquesGene OntologyGene SilencingGenes, HelminthGeneticsHeat StressHel-1 Protein, C. ElegansHelicase 1InsulinInsulin-Like Growth Factor IInsulin ReceptorInsulin/IGF-1IntestineIntestinesLifespanLongevityMammaliaMessenger RNAMetabolismMitochondrial RespirationMolecular GeneticsMolecular Sequence DataMutationNerve CellNeuronsNon-HumanNucleotide SequenceOxidative StressPhenotypePhysiologyPriority JournalProgenyProtein BindingPseudomonas AeruginosaReceptor, InsulinRegulatory MechanismReproductionRNA HelicaseRNA HelicasesRNA InterferenceRNA SequenceRNA, MessengerSequence AnalysisSequence Analysis, RNASignal TransductionSomatomedinSomatomedin 1Somatomedin CTranscription Factor Daf16Transcription Factor FOXOTransgeneUnclassified DrugUp-RegulationUpregulation
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


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