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

TitleRNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans.
Publication TypeJournal Article
Year of Publication2017
AuthorsSon, HG, Seo, M, Ham, S, Hwang, W, Lee, D, An, SWoo A, Artan, M, Seo, K, Kaletsky, R, Arey, RN, Ryu, Y, Ha, CMan, Kim, YKi, Murphy, CT, Roh, T-Y, Nam, HGil, Lee, S-JV
JournalNat Commun
Volume8
Pagination14749
Date Published2017 Mar 09
ISSN2041-1723
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.

DOI10.1038/ncomms14749
Alternate JournalNat Commun
PubMed ID28276441