Rogers, Aric N. et al. (2011) International Worm Meeting "Lifespan extension via eIF4G inhibition is mediated by post-transcriptional remodeling of stress response gene expression in C. elegans."

Kapahi, Pankaj, Hubbard, Alan, Melov, Simon, Chen, Di, Gibson, Bradford W., Rogers, Aric N., Felkey, Krysta, Lithgow, Gordon, McColl, Gawain, Czerwieniec, Gregg

[International Worm Meeting, 2011]

Reducing protein synthesis slows growth and development but can increase adult lifespan. We demonstrate that knock-down of eukaryotic translation initiation factor 4G (eIF4G), which is down-regulated during starvation, 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 lifespan extension when IFG-1 is inhibited and are novel determinants of longevity. 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 support a role for IFG-1 in mediating the antagonistic effects on growth and somatic maintenance by modulating translation of a specific class of mRNA based on transcript length.