摘要：SummaryNonsense-mediated mRNA decay (NMD) is a biological surveillance mechanism that eliminates mRNA transcripts with premature termination codons. InCaenorhabditis elegans, NMD contributes to longevity by enhancing RNA quality. Here, we aimed at identifying NMD-modulating factors that are crucial for longevity inC. elegansby performing genetic screens. We showed that knocking down each ofalgn-2/asparagine-linked glycosylation protein,zip-1/bZIP transcription factor, andC44B11.1/FAS apoptotic inhibitory molecule increased the transcript levels of NMD targets. Among these,algn-2exhibited an age-dependent decrease in its expression and was required for maintaining normal lifespan and for longevity caused by various genetic interventions. We further demonstrated that upregulation of ALGN-2 by inhibition ofdaf-2/insulin/IGF-1 receptor contributed to longevity in an NMD-dependent manner. Thus,algn-2, a positive regulator of NMD, plays a crucial role in longevity inC. elegans, likely by enhancing RNA surveillance. Our study will help understand how NMD-mediated mRNA quality control extends animal lifespan.Graphical AbstractDisplay OmittedHighlights•C. elegans algn-2is a positive regulator of nonsense-mediated mRNA decay (NMD)•algn-2is downregulated during aging and contributes to maintaining normal lifespan•algn-2is required for longevity caused by various genetic interventions•Upregulation of ALGN-2 by inhibition ofdaf-2promotes longevity via increasing NMDGenetics; Molecular Biology; Cell Biology
