title: RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea; School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea;
authors.forename: Mihwa
authors.initials: M
authors.lastname: Seo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea;
authors.forename: Keunhee
authors.initials: K
authors.lastname: Seo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea;
authors.forename: Wooseon
authors.initials: W
authors.lastname: Hwang
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea; School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea;
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Koo
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea;
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Hahm
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea;
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea;
authors.forename: Seong Kyu
authors.initials: SK
authors.lastname: Han
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea;
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea;
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea;
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea;
authors.forename: Yoontae
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea; nam@dgist.ac.kr seungjaelee@postech.ac.kr.
authors.forename: Hong Gil
authors.initials: HG
authors.lastname: Nam
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea; Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang 790-784, Korea nam@dgist.ac.kr seungjaelee@postech.ac.kr.
authors.forename: Seung-Jae V
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D017238:Genes, Helminth; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008136:Longevity; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D012098:Reproduction; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D012333:RNA, Messenger; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; C000602670:HEL-1 protein, C elegans; D020365:RNA Helicases
keywords: C. elegans; FOXO; RNA helicase; aging; insulin/IGF-1