RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. Elegans

Heehwa G. Son, Mihwa Seo, Seokjin Ham, Wooseon Hwang, Dongyeop Lee, Seon Woo A. An, Murat Artan, Keunhee Seo, Rachel Kaletsky, Rachel N. Arey, Youngjae Ryu, Chang Man Ha, Yoon Ki Kim, Coleen T. Murphy, Tae Young Roh, Hong Gil Nam, Seung Jae V. Lee

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Article number14749
JournalNature communications
Volume8
DOIs
StatePublished - Mar 9 2017

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Son, H. G., Seo, M., Ham, S., Hwang, W., Lee, D., An, S. W. A., Artan, M., Seo, K., Kaletsky, R., Arey, R. N., Ryu, Y., Ha, C. M., Kim, Y. K., Murphy, C. T., Roh, T. Y., Nam, H. G., & Lee, S. J. V. (2017). RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. Elegans. Nature communications, 8, [14749]. https://doi.org/10.1038/ncomms14749