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Nat Commun. 2017 Mar 9;8:14749. doi: 10.1038/ncomms14749.

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

Author information

1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
2
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
3
Center for Plant Aging Research, Institute for Basic Science, Daegu 42988, South Korea.
4
Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
5
Department of Molecular Biology &LSI Genomics, Princeton University, Princeton, New Jersey 08544, USA.
6
Research Division, Korea Brain Research Institute, Daegu 41068, South Korea.
7
Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, South Korea.
8
Division of Life Sciences, Korea University, Seoul 02841, South Korea.
9
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
10
Department of New Biology, DGIST, Daegu 42988, South Korea.

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.

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