title: Regulation of glucose-dependent gene expression by the RNA helicase Dbp2 in Saccharomyces cerevisiae.
abstract: Cellular homeostasis requires a fine balance between energy uptake, utilization, and growth. Dbp2 is a member of the DEAD-box protein family in Saccharomyces cerevisiae with characterized ATPase and helicase activity in vitro. DEAD-box RNA helicases are a class of enzymes that utilize ATP hydrolysis to remodel RNA and/or RNA-protein (RNP) composition. Dbp2 has been proposed to utilize its helicase activity in vivo to promote RNA-protein complex assembly of both messenger (m)RNAs and long noncoding (lnc)RNAs. Previous work from our laboratory demonstrated that loss of DBP2 enhances the lncRNA-dependent transcriptional induction of the GAL genes by abolishing glucose-dependent repression. Herein, we report that either a carbon source switch or glucose deprivation results in rapid export of Dbp2 to the cytoplasm. Genome-wide RNA sequencing identified a new class of antisense hexose transporter transcripts that are specifically upregulated upon loss of DBP2. Further investigation revealed that both sense and antisense hexose transporter (HXT) transcripts are aberrantly expressed in DBP2-deficient cells and that this expression pathway can be partially mimicked in wild-type cells by glucose depletion. We also find that Dbp2 promotes ribosome biogenesis and represses alternative ATP-producing pathways, as loss of DBP2 alters the transcript levels of ribosome biosynthesis (snoRNAs and associated proteins) and respiration gene products. This suggests that Dbp2 is a key integrator of nutritional status and gene expression programs required for energy homeostasis.
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-2063.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Beck
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-2063.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Cloutier
authors.affiliation: Next Generation Sequencing Core Facility, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schipma
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-2063.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Petell
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-2063 Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907-2064 Next Generation Sequencing Core Facility, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Wai Kit
authors.initials: WK
authors.lastname: Ma
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-2063 Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907-2064 ejtran@purdue.edu.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Tran
mesh_terms: D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D005800:Genes, Fungal; D005947:Glucose / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C438898:Dbp2 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D005947:Glucose
keywords: DEAD-box; helicase; metabolism; noncoding; transport