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 () and Seung-Jae V. Lee ()
Additional contact information
Heehwa G. Son: Pohang University of Science and Technology
Mihwa Seo: Pohang University of Science and Technology
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
Coleen T. Murphy: Princeton University
Tae-Young Roh: Pohang University of Science and Technology
Hong Gil Nam: Center for Plant Aging Research, Institute for Basic Science
Seung-Jae V. Lee: Pohang University of Science and Technology

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14749

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