ddr-2;rsks-1

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Genetic mutants with ddr-2, rsks-1 alterations

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

Temperature °C
20
Lifespan (days)
25.15
Lifespan change (compared to wild type)
35.51%
Phenotype
Over-expression of eIF4H/drr-2 did not have any effect on the lifespan of S6K/rsks-1 RNAi animals. Although S6K is known to act downstream of TOR to regulate translation by modulating the activity of several eIFs, this finding suggests that eIF4H/DRR-2 might be regulated by TOR via an S6K-independent pathway.
Lifespan comparisons
Double mutant ddr-2(OE);rsks-1(RNAi) has a lifespan of 25.15 days, while single mutant rsks-1(RNAi) has a lifespan of 25.33 days, single mutant ddr-2(OE) has a lifespan of 18.87 days and wild type has a lifespan of 18.56 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Temperature °C
20
Lifespan (days)
24.09
Lifespan change (compared to wild type)
26.66%
Phenotype
Over-expression of eIF4H/drr-2 did not have any effect on the lifespan of S6K/rsks-1 RNAi animals. Although S6K is known to act downstream of TOR to regulate translation by modulating the activity of several eIFs, this finding suggests that eIF4H/DRR-2 might be regulated by TOR via an S6K-independent pathway.
Lifespan comparisons
Double mutant ddr-2(OE);rsks-1(RNAi) has a lifespan of 24.09 days, while single mutant rsks-1(RNAi) has a lifespan of 22.77 days, single mutant ddr-2(OE) has a lifespan of 20.11 days and wild type has a lifespan of 19.02 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Search genes: ddr-2 rsks-1

Entrez ID
Symbol
GenAge
Wormbase ID

180622
ddr-2
View on GenAge (ddr-2)
WBGene00017381

Discoidin domain-containing receptor tyrosine kinase B

Locus: CELE_F11D5.3

Wormbase description: F11D5.3 encodes a putative tyrosine kinase homologous to human RS1 (OMIM:312700, mutated in juvenile X-linked retinoschisis).

Entrez ID
Symbol
GenAge
Wormbase ID

176554
rsks-1
View on GenAge (rsks-1)
WBGene00012929

Ribosomal protein S6 kinase beta

Locus: CELE_Y47D3A.16

Wormbase description: rsks-1 encodes a putative ribosomal protein S6 kinase (S6K) required additively with IFG-1 for normally high levels of protein synthesis, and for normally short lifespan; RSKS-1's effect on lifespan is independent of DAF-16, ISP-1, and SIR-2.1, and does not correlate with juglone resistance, but does correlate with abnormally high resistance to starvation and (perhaps) thermotolerance; RSKS-1 is required for normal juglone resistance, as well as normally rapid growth and normal brood sizes; RSKS-1 is expressed in E-lineage embryonic cells, and in pharyngeal and hypodermal cells of larvae and adults; RSKS-1 is orthologous to human RPS6KB1 (OMIM:608938) and RPS6KB2 (OMIM:608939).

Orthologs of ddr-2;rsks-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ddr1;Rps6kb1
Mus musculus	Ddr1;Rps6kb2
Mus musculus	Ddr2;Rps6kb1
Mus musculus	Ddr2;Rps6kb2
Mus musculus	Rps6kb1;Ddr1
Mus musculus	Rps6kb1;Ddr2
Mus musculus	Rps6kb2;Ddr1
Mus musculus	Rps6kb2;Ddr2

Orthologs of ddr-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ddr1
Mus musculus	Ddr2

Orthologs of rsks-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	S6k
Mus musculus	Rps6kb1
Mus musculus	Rps6kb2