title: RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans.
abstract: Long-lived organisms often feature more stringent protein and DNA quality control. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Here we show that NMD mediates longevity in C. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts. NMD components, including smg-2/UPF1, are required to achieve the longevity of several long-lived mutants, including daf-2 mutant worms. NMD in the nervous system of the animals is particularly important for RNA quality control to promote longevity. Furthermore, we find that downregulation of yars-2/tyrosyl-tRNA synthetase, an NMD target transcript, by daf-2 mutations contributes to longevity. We propose that NMD-mediated RNA surveillance is a crucial quality control process that contributes to longevity conferred by daf-2 mutations.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Heehwa G
authors.initials: HG
authors.lastname: Son
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.|School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.|Center for Plant Aging Research, Institute for Basic Science, Daegu 42988, South Korea.
authors.forename: Mihwa
authors.initials: M
authors.lastname: Seo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Seokjin
authors.initials: S
authors.lastname: Ham
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Wooseon
authors.initials: W
authors.lastname: Hwang
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Dongyeop
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Seon Woo A
authors.initials: SW
authors.lastname: An
authors.affiliation: Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Murat
authors.initials: M
authors.lastname: Artan
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Keunhee
authors.initials: K
authors.lastname: Seo
authors.affiliation: Department of Molecular Biology &LSI Genomics, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kaletsky
authors.affiliation: Department of Molecular Biology &LSI Genomics, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Arey
authors.affiliation: Research Division, Korea Brain Research Institute, Daegu 41068, South Korea.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Research Division, Korea Brain Research Institute, Daegu 41068, South Korea.
authors.forename: Chang Man
authors.initials: CM
authors.lastname: Ha
authors.affiliation: Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, South Korea.|Division of Life Sciences, Korea University, Seoul 02841, South Korea.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology &LSI Genomics, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Coleen T
authors.initials: CT
authors.lastname: Murphy
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.|Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Tae-Young
authors.identifier: 0000-0001-5833-0844
authors.initials: TY
authors.lastname: Roh
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science, Daegu 42988, South Korea.|Department of New Biology, DGIST, Daegu 42988, South Korea.
authors.forename: Hong Gil
authors.initials: HG
authors.lastname: Nam
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.|School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.|Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
authors.forename: Seung-Jae V
authors.initials: SV
authors.lastname: Lee
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D007328:Insulin / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D059365:Nonsense Mediated mRNA Decay; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D008164:Luminescent Proteins; D012333:RNA, Messenger; D012313:RNA; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin