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Next Generation Sequencing and Quantitative Analysis of mRNAs in Caenorhabditis elegans fbxl-5 Mutant Animals

ABSTRACT: The molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of the soma, remain poorly understood. We identified the C. elegans F-box protein FBXL-5 as a negative regulator of maternal provisioning of vitellogenin lipoproteins, which mediate the transfer of intestinal lipids to the germline. Mutations in fbxl-5 partially suppress the vitellogenesis defects observed in the heterochronic mutants lin-4 and lin-29, both of which ectopically express fbxl-5 at the adult developmental stage. FBXL-5 functions cell-autonomously to negatively regulate expression of the vitellogenin genes; and consistently, intestinal over-expression of FBXL-5 is sufficient to inhibit vitellogenesis, impair overall lipid homeostasis, and reduce lifespan. Our epistasis analyses suggest that fbxl-5 functions in concert with cul-6, a cullin gene, and the Skp1-related genes skr-3 and skr-5 to regulate vitellogenesis. Additionally, fbxl-5 acts genetically upstream of rict-1, which encodes the core mTORC2 protein Rictor, to govern vitellogenesis. Together, our results reveal an unexpected role for a SCF ubiquitin-ligase complex in controlling intestinal lipid homeostasis by tuning mTORC2 activity.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE248602 | GEO | 2023/12/01

REPOSITORIES: GEO

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