daf-16;mdt-15

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Genetic mutants with daf-16, mdt-15 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
25
Diet
NGM
Lifespan (days)
12.1
Lifespan change (compared to wild type)
-40.39%
Lifespan comparisons
Double mutant daf-16(mu86);mdt-15(RNAi) has a lifespan of 12.1 days, while single mutant mdt-15(RNAi) has a lifespan of 16.7 days, single mutant daf-16(mu86) has a lifespan of 13.1 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Almost additive (negative)
Citation
View abstract
Rogers AN et al., 2011, Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab. 14(1):55-66 21723504 Click here to select all mutants from this PubMed ID in the graph
Abstract
Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, 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 life span extension when IFG-1 is inhibited. 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 suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.

Search genes: daf-16 mdt-15

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Entrez ID
Symbol
GenAge
Wormbase ID

175817
mdt-15
View on GenAge (mdt-15)
WBGene00007016

Mediator of RNA polymerase II transcription subunit 15

Locus: CELE_R12B2.5

Wormbase description: mdt-15 encodes, by alternative splicing, two isoforms of a Mediator subunit orthologous to human MED15; together with NHR-49 and SBP-1, MDT-15 is required for normal fat accumulation, for expression of fatty acid (FA) desaturase genes (fat-5, fat-6, and fat-7), for normal levels of mono- and polyunsaturated FAs (PUFAs), and for viability, fecundity, mobility, and normally long lifespan; several of these phenotypes can be at least partially suppressed by supplying PUFAs in the food medium; in part through NHR-49, MDT-15 participates in basal and fasting-induced transcription of numerous other metabolic genes, such as gei-7 and acs-2; independently of NHR-49 and SBP-1, MDT-15 ensures appropriate transcriptional response and survival in response to toxins and heavy metals by inducing select detoxification genes encoding such as cdr-1, cyp-35C1, gst-5, mtl-1, mtl-2, ugt-1, ugt-8, and others; mdt-15 is expressed at constant levels from embryos to adulthood, in several head neurons and intestine; MDT-15 binds NHR-49 and NHR-64 in yeast two-hybrid assays, and SBP-1 in GST pull-down assays.

Orthologs of daf-16;mdt-15 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-16 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

Orthologs of mdt-15 in SynergyAge

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Species	Gene