title: Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans.
abstract: Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated with increased mRNA length. This association was supported by changes in the proteome assayed via quantitative mass spectrometry. Our results suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.
authors: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA. arogers@buckinstitute.org
authors: Aric N
authors: AN
authors: Rogers
authors: Di
authors: D
authors: Chen
authors: Gawain
authors: G
authors: McColl
authors: Gregg
authors: G
authors: Czerwieniec
authors: Krysta
authors: K
authors: Felkey
authors: Bradford W
authors: BW
authors: Gibson
authors: Alan
authors: A
authors: Hubbard
authors: Simon
authors: S
authors: Melov
authors: Gordon J
authors: GJ
authors: Lithgow
authors: Pankaj
authors: P
authors: Kapahi
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008136:Longevity / Q000235:genetics*; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D039603:Eukaryotic Initiation Factor-4G; D012333:RNA, Messenger