ifg-1;mdt-15

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Genetic mutants with ifg-1, 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)
18.5
Lifespan change (compared to wild type)
-18.14%
Lifespan comparisons
Double mutant ifg-1(cxTi9279);mdt-15(RNAi) has a lifespan of 18.5 days, while single mutant mdt-15(RNAi) has a lifespan of 17.7 days, single mutant ifg-1(cxTi9279) has a lifespan of 27.2 days and wild type has a lifespan of 22.6 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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.

Temperature °C
25
Diet
NGM
Lifespan (days)
16.0
Lifespan change (compared to wild type)
-21.18%
Lifespan comparisons
Double mutant ifg-1(cxTi9279);mdt-15(RNAi) has a lifespan of 16.0 days, while single mutant mdt-15(RNAi) has a lifespan of 16.7 days, single mutant ifg-1(cxTi9279) has a lifespan of 27.8 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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: ifg-1 mdt-15

Entrez ID
Symbol
GenAge
Wormbase ID

174322
ifg-1
View on GenAge (ifg-1)
WBGene00002066

Initiation Factor 4G (eIF4G) family

Locus: CELE_M110.4

Wormbase description: ifg-1 encodes, by alternative splicing, two orthologs of the translation initiation factor 4F, ribosome/mRNA-bridging subunit (eIF-4G); by homology, IFG-1 is predicted to function in poly(A) tail-dependent translation initiation; loss of ifg-1 activity in adult animals extends lifespan.

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 ifg-1;mdt-15 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of ifg-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	eIF4G2
Mus musculus	Eif4g1
Mus musculus	Eif4g3

Orthologs of mdt-15 in SynergyAge

Show in SynergyAge
Species	Gene