Attenuation of mRNA translation extends lifespan in metazoans by as yet unknown mechanisms. Eukaryotic translation initiation factor (eIF)-4G is an mRNA cap-binding complex member that positively regulates translation by acting as a scaffold between transcript 5'' and 3'' ends via eIF-4E and poly A binding protein, respectively. Here we show that reducing translation via suppression of eIF-4G (
ifg-1 in C. elegans) also differentially regulates expression of genes involved in responding to stress. Furthermore, we observe a positive correlation between mRNA size and translation as measured by ribosome loading when
ifg-1 is inhibited. This correlation extends to overall protein levels assayed using quantitative mass spectrometry. Genome-wide analysis shows that longer mRNAs are enriched with genes important for stress responses and that positively regulate lifespan and cellular homeostasis. Inhibition of some of these stress response genes substantially diminishes the increased lifespan under eIF-4G inhibition and include the FOXO transcription factor
daf-16 and the energy sensor AMP kinase catalytic subunit
aak-2. Expression of SCA-1, a Calcium ATPase involved in ER homeostasis, is essential for lifespan extension in an
ifg-1 mutant. Our results indicate that
ifg-1 controls a switch in mRNA translation between growth and development and somatic maintenance, which provides a novel mechanism for the tradeoffs between growth and longevity.