title: Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans.
abstract: The insulin-like signaling (ILS) pathway regulates metabolism and is known to modulate adult life span in C. elegans. Altered stress responses and resistance to a wide range of stressors are also associated with changes in ILS and contribute to enhanced longevity. The transcription factors DAF-16 and HSF-1 are key effectors of the longevity phenotype. We demonstrate that increased intrinsic thermotolerance, due to lower ILS, is not dependent on stress-induced transcriptional responses but instead requires active protein translation. Translation profiling experiments reveal genes that are posttranscriptionally regulated in response to altered ILS during heat shock in a DAF-16-dependent manner. Furthermore, several novel proteins are specifically required for ILS effects on thermotolerance. We propose that lowered ILS results in metabolic and physiological changes. These DAF-16-induced changes precondition a translational response under acute stress to modulate survival.
authors.affiliation: The Mental Health Research Institute, Parkville, Victoria, Australia. gmccoll@mhri.edu.au
authors.forename: Gawain
authors.initials: G
authors.lastname: McColl
authors.forename: Aric N
authors.initials: AN
authors.lastname: Rogers
authors.forename: Silvestre
authors.initials: S
authors.lastname: Alavez
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Link
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kapahi
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Lithgow
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D007328:Insulin / Q000378:metabolism*; D046228:Microarray Analysis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D007328:Insulin; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin
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