The role of Rsv1 in the transcriptional regulation of genes involved in sugar metabolism for long‐term survival

Abstract

Glucose limitation is a major stress condition that cells must respond to by altering their metabolism to ensure survival. Rsv1 is a zinc finger protein previously shown to be required for survival during stationary phase. In this study, we present a novel mechanism regulated by Rsv1 in the fission yeast Schizosaccharomyces pombe that is involved in altering glucose metabolic flux. We found that rsv1 gene expression is induced by Rst2 and Atf1, two transcription factors regulated by the cAMP‐dependent protein kinase (PKA) pathway and the mitogen‐activated protein kinase (MAPK) cascade, respectively. The downstream target genes of Rsv1 were identified by genome‐wide ChIP sequencing of Rsv1‐bound DNA sites and RNA sequencing analysis of Rsv1‐dependent transcripts that were differentially expressed under glucose starvation. Rsv1 directly regulated the expression of at least 21 genes that mostly encode transporters and proteins related to sugar metabolism. Among these, gcd1, which encodes glucose dehydrogenase in the gluconate shunt for the pentose phosphate pathway, was most remarkably repressed by Rsv1. The defect in survival of Δrsv1 mutant under glucose starvation condition was mitigated by additional deletion of a gcd1, idn1, or a gene for a putative lactonase (SPCC16c4.10), suggesting the critical importance of downregulating the gluconate shunt and pentose phosphate pathway for long‐term survival. These results show an intricate response to glucose starvation: increasing the synthesis of a transcription factor via two signal transduction pathways, which sheds light on the importance of remodeling a metabolic circuit to secure glucose for cell survival.

A new adaptation strategy to glucose starvation: modulation of the gluconate shunt and pentose phosphate pathway by the transcriptional repressor Rsv1

“…2). Interestingly, they show by ChIP that Atf1, Rst2, and Scr1 can be detected not only in the promoter of rsv1 but also in the 3' region of the gene [13]. This downstream position of the transcription factors could be related to the loop-formation hypothesis previously reported for the fbp1 gene [14], in which loops would be formed under glucose starvation conditions in order to induce nucleosome eviction and achieve full transcription.…”

“…Growth in low glucose conditions induces a number of metabolic adaptations such as a shift from fermentation to respiratory metabolism, or the activation of glucose uptake to promote long‐term survival. Among them, the regulation of the flux from glucose toward the PPP is tightly regulated, according to the work by Roe and colleagues . The molecular pathways and transcription factors involved in the regulation of each of these adaptation strategies, and the genes downstream of the pathways, are indicated (based on fission yeast).…”

“…The report by Kim and colleagues provides a mechanistic link between glucose deprivation and the regulation of the PPP. Thus, they show that the shortened life span of strain Δrsv1 is partially suppressed when enzymes from the gluconate shunt such as Gcd1 are removed.…”

“…In a very elegant study led by Jung‐Hye Roe published in The FEBS Journal , the role of the transcription factor Rsv1 in the regulation of glucose metabolism is analyzed, with a special focus on the regulation of the rsv1 gene and the consequences of its up‐regulation during glucose starvation. Rsv1 is homologous to Aspergillus nidulans CreA, Saccharomyces cerevisiae Mig1, and mammalian EGR‐1/NGFI‐A , and is synthesized only in low glucose environments, based on the work by the Roe laboratory. They describe the transcriptional up‐regulation of rsv1 during glucose starvation, demonstrating that it depends on the Sty1‐Atf1 cascade and also on the Scr1 and Rst2 transcription factors, resembling the well‐known regulation of fbp1 (Fig.…”

Enzyme production ofd-gluconic acid and glucose oxidase: successful tales of cascade reactions

“…2 The derivation of glucose between these two metabolic alternatives, glycolysis and PPP, depends on the environmental situation (the nutrient concentration and presence or absence of stressors). 1,3 In the gluconate shunt, glucose is oxidized by glucose dehydrogenase to furnish gluconate, the form in which D-gluconic acid is present at physiological pH. Subsequently, gluconate is phosphorylated by the action of gluconate kinase to produce 6-phosphogluconate, which is the second intermediate of the pentose phosphate pathway (Fig.…”