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McColl, G, Rogers, AN, Alavez, S, Hubbard, AE, Melov, S, Link, CD, Bush, AI, Kapahi, P and Lithgow, GJ (2010) Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans. Cell Metab. 12:260-72


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.


PubMed PMC2945254 Online version:10.1016/j.cmet.2010.08.004


Animals; Caenorhabditis elegans/genetics; Caenorhabditis elegans/physiology; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Heat-Shock Proteins/genetics; Heat-Shock Proteins/metabolism; Hot Temperature; Insulin/metabolism; Microarray Analysis; Promoter Regions, Genetic; RNA, Messenger/genetics; RNA, Messenger/metabolism; Receptor, Insulin/genetics; Receptor, Insulin/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Ribosomes/metabolism; Signal Transduction/physiology; Stress, Physiological/physiology; Survival Rate; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

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