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Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans
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Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans
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Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans
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Journal Article
Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans
2022
Overview
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 (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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Aging
/ Animal Genetics and Genomics
/ Animals
/ Biomedical and Life Sciences
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans Proteins - genetics
/ Fatty Acid Desaturases - genetics
/ Genes
/ Genomics
/ Insects
/ Insulin
/ Insulin-like growth factor I
/ Kinases
/ Microbial Genetics and Genomics
/ Mutants
/ Protein Serine-Threonine Kinases - genetics
/ Protein-Tyrosine Kinases - genetics
/ RNA-seq
/ Worms
