In:
BMC Genomics, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-01-04)
Abstract:
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 (H 2 S), 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 H 2 S metabolic-genes. These roles are only partially dependent on genetic background. Considering the particular importance of fatty acid desaturation and H 2 S 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.
Type of Medium:
Online Resource
ISSN:
1471-2164
DOI:
10.1186/s12864-021-08176-y
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2041499-7
SSG:
12
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