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

Author

Listed:
  • Heehwa G. Son

    (Pohang University of Science and Technology)

  • Mihwa Seo

    (Pohang University of Science and Technology
    School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology
    Center for Plant Aging Research, Institute for Basic Science)

  • Seokjin Ham

    (Pohang University of Science and Technology)

  • Wooseon Hwang

    (Pohang University of Science and Technology)

  • Dongyeop Lee

    (Pohang University of Science and Technology)

  • Seon Woo A. An

    (Pohang University of Science and Technology)

  • Murat Artan

    (Information Technology Convergence Engineering, Pohang University of Science and Technology)

  • Keunhee Seo

    (Pohang University of Science and Technology)

  • Rachel Kaletsky

    (Princeton University)

  • Rachel N. Arey

    (Princeton University)

  • Youngjae Ryu

    (Korea Brain Research Institute)

  • Chang Man Ha

    (Korea Brain Research Institute)

  • Yoon Ki Kim

    (Creative Research Initiatives Center for Molecular Biology of Translation, Korea University
    Korea University)

  • Coleen T. Murphy

    (Princeton University)

  • Tae-Young Roh

    (Pohang University of Science and Technology
    Pohang University of Science and Technology)

  • Hong Gil Nam

    (Center for Plant Aging Research, Institute for Basic Science
    DGIST)

  • Seung-Jae V. Lee

    (Pohang University of Science and Technology
    School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology
    Information Technology Convergence Engineering, Pohang University of Science and Technology)

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.

Suggested Citation

  • 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 & Col, 2017. "RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14749
    DOI: 10.1038/ncomms14749
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