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A dicer-related helicase opposes the age-related pathology from SKN-1 activation in ASI [ChIP-seq]

ABSTRACT: Coordination of cellular responses to stress are essential for health across the lifespan. The transcription factor SKN-1 is an essential homeostat that mediates survival in stress-inducing environments and cellular dysfunction, but constitutive activation of SKN-1 drives premature aging thus revealing the importance of turning off cytoprotective pathways. Here we identify how SKN-1 activation in two ciliated ASI neurons in C. elegans results in an increase in organismal transcriptional capacity that drives pleiotropic outcomes in peripheral tissues. An increase in the expression of established SKN-1 stress response and lipid metabolism gene classes of RNA in the ASI neurons, in addition to the increased expression of several classes of non-coding RNA, define a molecular signature of animals with constitutive SKN-1 activation and diminished healthspan. We reveal neddylation as a novel regulator of the SKN-1 homeostat that mediates SKN-1 abundance within intestinal cells. Moreover, RNAi-independent activity of the dicer-related DExD/H-box helicase, drh-1, in the intestine, can oppose the effects of aberrant SKN-1 transcriptional activation and delays age-dependent decline in health. Taken together, our results uncover a cell non-autonomous circuit to maintain organism-level homeostasis in response to excessive SKN-1 transcriptional activity in the sensory nervous system.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE246466 | GEO | 2023/12/06

REPOSITORIES: GEO

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Project description:Boar taint is an offensive odour and flavour from developed in a proportion of non-castrated male pigs (boars). Surgical castration is an effective solution but is under debate due to animal welfare concerns. Gene-based selection for low boar taint has been proposed as concentrations of the main compounds responsible for boar taint (androstenone, skatole and indole [ASI]) exhibit heritability but candidate biomarkers are lacking. The aims of this study were to identify expression quantitative trait loci (eQTLs) associated with ASI in order to aid development of candidate biomarkers and to generate insights into biological pathways. Gene expression profiles were obtained by RNA-Seq from testis of Danish Duroc × Landrace/Yorkshire boars fed either a control or chicory-added diet and genotyping was conducted with a high density SNP panel. A tendency (P = 0.052) of lowered ASI concentrations was found in the chicory group. Furthermore, a high correlation was found between estimated breeding values (EBVs) of androstenone and androstenone concentrations (r2 = 0.48). A total of 213 eQTLs, representing 125 unique genes including MVP, COX1, MAP2K4 and RDH16, contained genotypes associated with summed ASI concentrations and of these, six genes were also differentially expressed across ASI/diet groups. The genes were functionally associated with membrane localised proteins, extracellular exosomes, ATP binding, MAPK cascade and oxidative stress. The highest densities of the eQTLs were on pig chromosomes (SSC) SSC18, SSC12, SSC2, SSC7 and SSC14, in that order. A total of 42 known porcine traits were enriched by the genomic coordinates, including health, meat quality and one reproduction trait. A total of 33 candidate eQTLs enriched known genomic coordinates for androstenone and odour intensity in fat. Our findings suggests that careful monitoring of important productions parameters is necessary, if gene-based selection is performed with markers located within the genomic coordinates of the candidate eQTLs or the eQTLs themselves.

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A dicer-related helicase opposes the age-related pathology from SKN-1 activation in ASI [ChIP-seq]

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