Abstract
BackgroundIn the nematode Caenorhabditis elegans, longevity in response to germline ablation, but not in response to reduced insulin/IGF1-like signaling, is strongly dependent on the conserved protein kinase minibrain-related kinase 1 (MBK-1). In humans, the MBK-1 ortholog DYRK1A is associated with a variety of disorders, most prominently with neurological defects observed in Down syndrome. To better understand mbk-1’s physiological roles and their dependence on genetic background, we analyzed the influence of mbk-1 loss on the transcriptomes of wildtype and long-lived, germline-deficient or insulin-receptor defective, C. elegans strains by RNA-sequencing.Resultsmbk-1 loss elicited global changes in transcription that were less pronounced in insulin-receptor mutant than in germline-deficient or wildtype C. elegans. Irrespective of genetic background, mbk-1 regulated genes were enriched for functions in biological processes related to organic acid metabolism and pathogen defense. qPCR-studies confirmed mbk-1 dependent induction of all three C. elegans Δ9-fatty acid desaturases, fat-5, fat-6 and fat-7, in wildtype, germline-deficient and insulin-receptor mutant strains. Conversely, mbk-1 dependent expression patterns of selected pathogen resistance genes, including asp-12, dod-24 and drd-50, differed across the genetic backgrounds examined. Finally, cth-1 and cysl-2, two genes which connect pathogen resistance to the metabolism of the gaseous messenger and lifespan regulator hydrogen sulfide (H2S), were commonly suppressed by mbk-1 loss only in wildtype and germline-deficient, but not in insulin-receptor mutant C. elegans.ConclusionOur work reveals previously unknown roles of C. elegans mbk-1 in the regulation of fatty acid desaturase- and H2S metabolic-genes. These roles are only partially dependent on genetic background. Considering the particular importance of fatty acid desaturation and H2S for longevity of germline-deficient C. elegans, we propose that these processes at least in part account for the previous observation that mbk-1 preferentially regulates lifespan in these worms.
Highlights
Caenorhabditis elegans mbk-1 encodes an evolutionarily conserved dual-specificity tyrosine-regulated kinase (DYRK) orthologous to Drosophila melanogaster minibrain and human DYRK1A/B [1,2,3,4]
Loss of mbk‐1 decreases heat and oxidative stress resistance in germline‐deficient worms We previously reported that the longevity of germline stem cells (GSCs) deficient C. elegans is strongly dependent on mbk-1 [13]
As changes in longevity are frequently accompanied by changes in resistance to environmental stress such as heat or oxidative stress [23], we examined how mbk-1 influences these properties in GSC(−), daf-2(−) and corresponding GSC(+) or daf-2(+) control worms
Summary
Caenorhabditis elegans mbk-1 (minibrain-related kinase 1) encodes an evolutionarily conserved dual-specificity tyrosine-regulated kinase (DYRK) orthologous to Drosophila melanogaster minibrain and human DYRK1A/B [1,2,3,4]. In the nematode Caenorhabditis elegans, longevity in response to germline ablation, but not in response to reduced insulin/IGF1-like signaling, is strongly dependent on the conserved protein kinase minibrainrelated kinase 1 (MBK-1). The MBK-1 ortholog DYRK1A is associated with a variety of disorders, most promi‐ nently with neurological defects observed in Down syndrome. To better understand mbk-1’s physiological roles and their dependence on genetic background, we analyzed the influence of mbk-1 loss on the transcriptomes of wildtype and long-lived, germline-deficient or insulin-receptor defective, C. elegans strains by RNA-sequencing
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