daf-2;prmt-1

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Genetic mutants with daf-2, prmt-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)
22.9
Lifespan comparisons
Double mutant daf-2(e1368);prmt-1(ok2710) has a lifespan of 22.9 days, while single mutant daf-2(e1368) has a lifespan of 29.1 days.
Citation
View abstract
Takahashi Y et al., 2011, Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16. Cell Metab. 13(5):505-16 21531333 Click here to select all mutants from this PubMed ID in the graph
Abstract
Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). It is well established that PRMTs are implicated in various cellular processes, but their physiological roles remain unclear. Using nematodes with a loss-of-function mutation, we show that prmt-1, the major asymmetric arginine methyltransferase, is a positive regulator of longevity in C. elegans. This regulation is dependent on both its enzymatic activity and DAF-16/FoxO transcription factor, which is negatively regulated by AKT-mediated phosphorylation downstream of the DAF-2/insulin signaling. prmt-1 is also required for stress tolerance and fat storage but not dauer formation in daf-2 mutants. Biochemical analyses indicate that PRMT-1 methylates DAF-16, thereby blocking its phosphorylation by AKT. Disruption of PRMT-1 induces phosphorylation of DAF-16 with a concomitant reduction in the expression of longevity-related genes. Thus, we provide a mechanism by which asymmetric arginine dimethylation acts as an antiaging modification in C. elegans.

Temperature °C
20
Diet
OP50
Lifespan (days)
21.2
Lifespan comparisons
Double mutant daf-2(e1368);prmt-1(ok2710) has a lifespan of 21.2 days, while single mutant daf-2(e1368) has a lifespan of 27.7 days.
Citation
View abstract
Takahashi Y et al., 2011, Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16. Cell Metab. 13(5):505-16 21531333 Click here to select all mutants from this PubMed ID in the graph
Abstract
Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). It is well established that PRMTs are implicated in various cellular processes, but their physiological roles remain unclear. Using nematodes with a loss-of-function mutation, we show that prmt-1, the major asymmetric arginine methyltransferase, is a positive regulator of longevity in C. elegans. This regulation is dependent on both its enzymatic activity and DAF-16/FoxO transcription factor, which is negatively regulated by AKT-mediated phosphorylation downstream of the DAF-2/insulin signaling. prmt-1 is also required for stress tolerance and fat storage but not dauer formation in daf-2 mutants. Biochemical analyses indicate that PRMT-1 methylates DAF-16, thereby blocking its phosphorylation by AKT. Disruption of PRMT-1 induces phosphorylation of DAF-16 with a concomitant reduction in the expression of longevity-related genes. Thus, we provide a mechanism by which asymmetric arginine dimethylation acts as an antiaging modification in C. elegans.

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

Temperature °C
20
Diet
OP50
Lifespan (days)
36.4
Lifespan change (compared to wild type)
141.06%
Lifespan comparisons
Double mutant daf-2(e1370);prmt-1(ok2710) has a lifespan of 36.4 days, while single mutant daf-2(e1370) has a lifespan of 38.2 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Takahashi Y et al., 2011, Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16. Cell Metab. 13(5):505-16 21531333 Click here to select all mutants from this PubMed ID in the graph
Abstract
Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). It is well established that PRMTs are implicated in various cellular processes, but their physiological roles remain unclear. Using nematodes with a loss-of-function mutation, we show that prmt-1, the major asymmetric arginine methyltransferase, is a positive regulator of longevity in C. elegans. This regulation is dependent on both its enzymatic activity and DAF-16/FoxO transcription factor, which is negatively regulated by AKT-mediated phosphorylation downstream of the DAF-2/insulin signaling. prmt-1 is also required for stress tolerance and fat storage but not dauer formation in daf-2 mutants. Biochemical analyses indicate that PRMT-1 methylates DAF-16, thereby blocking its phosphorylation by AKT. Disruption of PRMT-1 induces phosphorylation of DAF-16 with a concomitant reduction in the expression of longevity-related genes. Thus, we provide a mechanism by which asymmetric arginine dimethylation acts as an antiaging modification in C. elegans.

Temperature °C
20
Diet
OP50
Lifespan (days)
39.0
Lifespan change (compared to wild type)
142.24%
Lifespan comparisons
Double mutant daf-2(e1370);prmt-1(ok2710) has a lifespan of 39.0 days, while single mutant daf-2(e1370) has a lifespan of 40.0 days and wild type has a lifespan of 16.1 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Takahashi Y et al., 2011, Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16. Cell Metab. 13(5):505-16 21531333 Click here to select all mutants from this PubMed ID in the graph
Abstract
Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). It is well established that PRMTs are implicated in various cellular processes, but their physiological roles remain unclear. Using nematodes with a loss-of-function mutation, we show that prmt-1, the major asymmetric arginine methyltransferase, is a positive regulator of longevity in C. elegans. This regulation is dependent on both its enzymatic activity and DAF-16/FoxO transcription factor, which is negatively regulated by AKT-mediated phosphorylation downstream of the DAF-2/insulin signaling. prmt-1 is also required for stress tolerance and fat storage but not dauer formation in daf-2 mutants. Biochemical analyses indicate that PRMT-1 methylates DAF-16, thereby blocking its phosphorylation by AKT. Disruption of PRMT-1 induces phosphorylation of DAF-16 with a concomitant reduction in the expression of longevity-related genes. Thus, we provide a mechanism by which asymmetric arginine dimethylation acts as an antiaging modification in C. elegans.

Search genes: daf-2 prmt-1

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Entrez ID
Symbol
GenAge
Wormbase ID

180326
prmt-1
View on GenAge (prmt-1)
WBGene00013766

Protein arginine N-methyltransferase 1

Locus: CELE_Y113G7B.17

Wormbase description: prmt-1 encodes a type I protein arginine methyltransferase; in C. elegans, PRMT-1 positively regulates adult lifespan and is required for stress response and fat storage in the absence of DAF-2-mediated signaling; PRMT-1 is also required for proper development of myofilament structure; PRMT-1 physically interacts with, and methylates, DAF-16 thereby preventing its phosphorylation and cytoplasmic retention; in body wall muscle cells, PRMT-1 has been localized to the endoplasmic reticulum.

Orthologs of daf-2;prmt-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Art1;InR
Mus musculus	Insr;Prmt8
Mus musculus	Insr;Prmt1
Mus musculus	Igf1r;Prmt8
Mus musculus	Igf1r;Prmt1
Mus musculus	Insrr;Prmt8
Mus musculus	Insrr;Prmt1

Orthologs of daf-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr

Orthologs of prmt-1 in SynergyAge

Show in SynergyAge
Species	Gene