RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans. Author Heehwa Son, Mihwa Seo, Seokjin Ham, Wooseon Hwang, Dongyeop Lee, Seon An, Murat Artan, Keunhee Seo, Rachel Kaletsky, Rachel Arey, Youngjae Ryu, Chang Ha, Yoon Kim, Coleen Murphy, Tae-Young Roh, Hong Nam, Seung-Jae Lee Publication Year 2017 Type Journal Article 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. Keywords Animals, Gene Expression Profiling, RNA, Messenger, Caenorhabditis elegans, Mutation, RNA, Luminescent Proteins, Animals, Genetically Modified, Caenorhabditis elegans Proteins, Insulin, Longevity, Receptor, Insulin, Insulin-Like Growth Factor I, Nonsense Mediated mRNA Decay Journal Nat Commun Volume 8 Pages 14749 Date Published 2017 Mar 09 ISSN Number 2041-1723 DOI 10.1038/ncomms14749 Alternate Journal Nat Commun PMCID PMC5347137 PMID 28276441 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML