Metabolic Adaptation to Nutrients Involves Co-regulation of Gene Expression by the RNA Helicase Dbp2 and the Cyc8 Co-repressor in Saccharomyces cerevisiae

Cells fine-tune their metabolic programs according to nutrient availability in order to maintain homeostasis. This is achieved largely through integrating signaling pathways and the gene expression program, allowing cells to adapt to nutritional change. Dbp2, a member of the DEAD-box RNA helicase family in Saccharomyces cerevisiae, has been proposed to integrate gene expression with cellular metabolism. Prior work from our laboratory has reported the necessity of DBP2 in proper gene expression, particularly for genes involved in glucose-dependent regulation. Here, by comparing differentially expressed genes in dbp2 to those of 700 other deletion strains from other studies, we find that CYC8 and TUP1, which form a complex and inhibit transcription of numerous genes, co-repress a common set of genes with DBP2. GO annotations reveal that these co-repressed genes are related to cellular metabolism, including respiration, gluconeogenesis, and alternative carbon source utilization genes. Consistent with a direct role in metabolic gene regulation, loss of either DBP2 or CYC8 results in increased cellular respiration rates. Furthermore, we find that co-repressed genes have a propensity to be associated with overlapping long non-coding RNAs and that up-regulation of these genes in the absence of DBP2 correlates with decreased binding of Cyc8 to these gene promoters. Taken together, this suggests that Dbp2 integrates nutrient availability with energy homeostasis by maintaining repression of glucose-repressed, Cyc8-targeted genes across the genome.

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