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

• Published in: Nature communications Vol. 8; no. 1; p. 14749
• Main Authors: Son, Heehwa G., Seo, Mihwa, Ham, Seokjin, Hwang, Wooseon, Lee, Dongyeop, An, Seon Woo A., Artan, Murat, Seo, Keunhee, Kaletsky, Rachel, Arey, Rachel N., Ryu, Youngjae, Ha, Chang Man, Kim, Yoon Ki, Murphy, Coleen T., Roh, Tae-Young, Nam, Hong Gil, Lee, Seung-Jae V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-03-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/89; 14/19; 14/35; 14/63; 45/91; 631/1647/334/1582/712; 631/337/1645/2020; 631/443/7; 64/11; Aging; Alzheimer's disease; Animals; Animals, Genetically Modified; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Gene Expression Profiling; Humanities and Social Sciences; Insulin; Insulin - genetics; Insulin-Like Growth Factor I - genetics; Insulin-like growth factors; Life sciences; Longevity - genetics; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Molecular biology; multidisciplinary; Mutation; Nonsense Mediated mRNA Decay; Proteins; Quality control; Receptor, Insulin - genetics; RNA - genetics; RNA - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Surveillance; Transfer RNA; South Korea
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14749

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.
The decline of DNA and protein quality control contributes to organismal ageing. Here, Son
et al
. report that nonsense-mediated mRNA decay, a RNA quality control mechanism, is enhanced in long-lived
daf-2
mutant worms and contributes to their longevity by regulating expression of the
yars-2
/tyrosyl tRNA synthetase.