RRC ID 53336
Author Cattie DJ, Richardson CE, Reddy KC, Ness-Cohn EM, Droste R, Thompson MK, Gilbert WV, Kim DH.
Title Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans.
Journal PLoS Genet
Abstract The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory roles. Here, we show that loss-of-function mutations in the genes encoding the conserved eIF3k and eIF3l subunits of the translation initiation complex eIF3 result in a 40% extension in lifespan and enhanced resistance to endoplasmic reticulum (ER) stress in Caenorhabditis elegans. In contrast to previously described mutations in genes encoding translation initiation components that confer lifespan extension in C. elegans, loss-of-function mutations in eif-3.K or eif-3.L are viable, and mutants show normal rates of growth and development, and have wild-type levels of bulk protein synthesis. Lifespan extension resulting from EIF-3.K or EIF-3.L deficiency is suppressed by a mutation in the Forkhead family transcription factor DAF-16. Mutations in eif-3.K or eif-3.L also confer enhanced resistance to ER stress, independent of IRE-1-XBP-1, ATF-6, and PEK-1, and independent of DAF-16. Our data suggest a pivotal functional role for conserved eIF3k and eIF3l accessory subunits of eIF3 in the regulation of cellular and organismal responses to ER stress and aging.
Volume 12(9)
Pages e1006326
Published 2016-9-1
DOI 10.1371/journal.pgen.1006326
PMID 27690135
PMC PMC5045169
MeSH Adaptation, Physiological / genetics Aging / genetics Animals Animals, Genetically Modified Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins / genetics* Endoplasmic Reticulum Stress / genetics* Eukaryotic Initiation Factor-3 / genetics* Longevity / genetics* Microtubule-Associated Proteins / genetics* Mutation Stress, Physiological / genetics
IF 5.175
Times Cited 13
C.elegans tm2482