Background: 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 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.
Results: mbk-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 (HS), were commonly suppressed by mbk-1 loss only in wildtype and germline-deficient, but not in insulin-receptor mutant C. elegans.
Conclusion: Our work reveals previously unknown roles of C. elegans mbk-1 in the regulation of fatty acid desaturase- and HS metabolic-genes. These roles are only partially dependent on genetic background. Considering the particular importance of fatty acid desaturation and HS 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.
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http://dx.doi.org/10.1186/s12864-021-08176-y | DOI Listing |
Stem Cells Dev
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Department of Clinical Pharmacy and Pharmacy Practices, Faculty of Pharmacy, University Malaya, Kuala Lumpur, Malaysia.
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Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, 150030, China.
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Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
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Tokat Gaziosmanpasa University Faculty of Arts and Sciences: Tokat Gaziosmanpasa Universitesi Fen Edebiyat Fakultesi, Biology, Tokat, Tokat, TURKEY.
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