rrf-3;skn-1

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Genetic mutants with rrf-3, skn-1 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
20.43
Lifespan change (compared to wild type)
-0.05%
Lifespan comparisons
Double mutant rrf-3(pk1426);skn-1(RNAi) has a lifespan of 20.43 days, while single mutant rrf-3(pk1426) has a lifespan of 19.53 days and wild type has a lifespan of 20.44 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Tullet JM et al., 2008, Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 132(6):1025-38 18358814 Click here to select all mutants from this PubMed ID in the graph
Abstract
Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IIS-inhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress by mobilizing the conserved phase 2 detoxification response. Here we show that IIS not only opposes DAF-16 but also directly inhibits SKN-1 in parallel. The IIS kinases AKT-1, -2, and SGK-1 phosphorylate SKN-1, and reduced IIS leads to constitutive SKN-1 nuclear accumulation in the intestine and SKN-1 target gene activation. SKN-1 contributes to the increased stress tolerance and longevity resulting from reduced IIS and delays aging when expressed transgenically. Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS.

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

Temperature °C
25
Diet
OP50
Lifespan (days)
9.3
Lifespan change (compared to wild type)
-32.61%
Lifespan comparisons
Double mutant rrf-3(pk1426);skn-1(zu129) has a lifespan of 9.3 days, while wild type has a lifespan of 13.8 days.
Type of interaction
See methods
Partially known monotony. Negative epistasis
Citation
View abstract
Tullet JM et al., 2008, Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 132(6):1025-38 18358814 Click here to select all mutants from this PubMed ID in the graph
Abstract
Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IIS-inhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress by mobilizing the conserved phase 2 detoxification response. Here we show that IIS not only opposes DAF-16 but also directly inhibits SKN-1 in parallel. The IIS kinases AKT-1, -2, and SGK-1 phosphorylate SKN-1, and reduced IIS leads to constitutive SKN-1 nuclear accumulation in the intestine and SKN-1 target gene activation. SKN-1 contributes to the increased stress tolerance and longevity resulting from reduced IIS and delays aging when expressed transgenically. Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS.

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

Temperature °C
25
Diet
OP50
Lifespan (days)
12.0
Lifespan change (compared to wild type)
-13.04%
Lifespan comparisons
Double mutant rrf-3(pk1426);skn-1(zu135) has a lifespan of 12.0 days, while wild type has a lifespan of 13.8 days.
Type of interaction
See methods
Partially known monotony. Negative epistasis
Citation
View abstract
Tullet JM et al., 2008, Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 132(6):1025-38 18358814 Click here to select all mutants from this PubMed ID in the graph
Abstract
Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IIS-inhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress by mobilizing the conserved phase 2 detoxification response. Here we show that IIS not only opposes DAF-16 but also directly inhibits SKN-1 in parallel. The IIS kinases AKT-1, -2, and SGK-1 phosphorylate SKN-1, and reduced IIS leads to constitutive SKN-1 nuclear accumulation in the intestine and SKN-1 target gene activation. SKN-1 contributes to the increased stress tolerance and longevity resulting from reduced IIS and delays aging when expressed transgenically. Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS.

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

Temperature °C
25
Diet
OP50
Lifespan (days)
7.2
Lifespan change (compared to wild type)
-47.83%
Lifespan comparisons
Double mutant rrf-3(pk1426);skn-1(zu67) has a lifespan of 7.2 days, while wild type has a lifespan of 13.8 days.
Type of interaction
See methods
Partially known monotony. Negative epistasis
Citation
View abstract
Tullet JM et al., 2008, Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 132(6):1025-38 18358814 Click here to select all mutants from this PubMed ID in the graph
Abstract
Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IIS-inhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress by mobilizing the conserved phase 2 detoxification response. Here we show that IIS not only opposes DAF-16 but also directly inhibits SKN-1 in parallel. The IIS kinases AKT-1, -2, and SGK-1 phosphorylate SKN-1, and reduced IIS leads to constitutive SKN-1 nuclear accumulation in the intestine and SKN-1 target gene activation. SKN-1 contributes to the increased stress tolerance and longevity resulting from reduced IIS and delays aging when expressed transgenically. Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS.

Search genes: rrf-3 skn-1

Entrez ID
Symbol
GenAge
Wormbase ID

174315
rrf-3
View on GenAge (rrf-3)
WBGene00004510

RNA-dependent RNA polymerase Family

Locus: CELE_F10B5.7

Wormbase description: rrf-3 encodes an RNA-directed RNA polymerase (RdRP) homolog that inhibits somatic RNAi, and thus promotes activity of repeated genes (e.g., multicopy transgenic arrays); the effect of RRF-3 on RNAi is opposite to that of RRF-1 (which stimulates somatic RNAi), which might arise from competition by RRF-3 with RRF-1 or EGO-1 in RNAi formation; rrf-3(allele) or rrf-3(allele2) mutants are hypersensitive to somatic RNAi, and conversely suppress the activity of an integrated rol6 (su1006) transgene.

Entrez ID
Symbol
GenAge
Wormbase ID

177343
skn-1
View on GenAge (skn-1)
WBGene00004804

Protein skinhead-1;SKiNhead

Locus: CELE_T19E7.2

Wormbase description: skn-1 encodes a bZip transcription factor orthologous to the mammalian Nrf (Nuclear factor-erythroid-related factor) transcription factors; during early embryogenesis, maternally provided SKN-1 is required for specification of the EMS blastomere, a mesendodermal precursor that gives rise to pharyngeal, muscle, and intestinal cells; later, during postembryonic development, SKN-1 functions in the p38 MAPK pathway to regulate the oxidative stress response and in parallel to DAF-16/FOXO in the DAF-2-mediated insulin/IGF-1-like signaling pathway to regulate adult lifespan; in vitro assays indicate that SKN-1 can be directly phosphorylated by the AKT-1, AKT-2, and SGK-1 kinases that lie downstream of DAF-2 in the insulin signaling pathway and in vivo experiments suggest that this phosphorylation is essential for regulation of SKN-1 nuclear accumulation and hence, transcriptional regulator activity; in the early embryo, SKN-1 is detected at highest levels in nuclei of the P1 blastomere and its descendants through the 8-cell stage of embryogenesis; later in embryogenesis, SKN-1 is observed in all hypodermal and intestinal nuclei, with reporter constructs indicating that intestinal expression begins as early as the 50-100-cell stage; in larvae and young adults, SKN-1::GFP reporters are expressed in the intestine and ASI neurons, with expression in intestinal nuclei enhanced under conditions of stress or reduced DAF-2 signaling.

Orthologs of rrf-3;skn-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of rrf-3 in SynergyAge

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Species	Gene

Orthologs of skn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Nfe2
Mus musculus	Nfe2l2
Mus musculus	Nfe2l1