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Transcriptome analyses of pdr5Dyor1D mutant in yeasts

ABSTRACT: ATP-binding cassette transporters Pdr5 and Yor1 from Saccharomyces cerevisiae control the asymmetric distribution of phospholipids across the plasma membrane as well as serving as ATP-dependent drug efflux pumps. Mutant strains lacking these transporter proteins were found to exhibit very different resistant phenotypes to two inhibitors of sphingolipid biosynthesis that act either late (aureobasidin A:AbA) or early (myriocin: Myr) in the pathway leading to production of these important plasma membrane lipids. These pdr5D yor1 strains were highly AbA resistant but extremely sensitive to Myr. We provide evidence that these phenotypic changes are likely due to modulation of the plasma membrane flippase complexes: Dnf1/Lem3 and Dnf2/Lem3. Flippases act to move phospholipids from the outer to the inner leaflet of the plasma membrane. Genetic analyses indicate that lem3D mutant strains are highly AbA sensitive and Myr resistant. These phenotypes are fully epistatic to those seen in pdr5D yor1 strains. Direct analysis of AbA-induced signaling demonstrated that loss of Pdr5 and Yor1 inhibited the AbA-triggered phosphorylation of the AGC kinase Ypk1 and its substrate Orm1. Microarray experiments found that a pdr5D yor1 strain induced a Pdr1-dependent induction of the entire Pdr regulon. Our data support the view that Pdr5/Yor1 negatively regulate flippase function and activity of the nuclear Pdr1 transcription factor. Together, these data argue that the interaction of the ABC transporters Pdr5 and Yor1 with the Lem3-dependent flippases regulate permeability of AbA via control of plasma membrane protein function as seen for the high-affinity tryptophan permease Tat2.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE65264 | GEO | 2015/01/24

SECONDARY ACCESSION(S): PRJNA273515

REPOSITORIES: GEO

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Project description:The yeast Saccharomyces cerevisiae is able to adapt and in situ detoxify lignocellulose derived inhibitors such as furfural and HMF. The length of lag phase for cell growth in response to the inhibitor challenge has been used to measure tolerance of strain performance. Mechanisms of yeast tolerance at the genome level remain unknown. Using systems biology approache, this study investigated comparative transcriptome profiling, metabolic profiling, cell growth response and gene regulatory interactions of yeast strains and selective gene deletion mutations in response to HMF challenges during the lag phase of growth. Three hundred and sixty-five candidate genes were identified and found at least three significant components involving some of these genes that enable yeast adaptation and tolerance to HMF in yeast. First, functional enzyme coding genes such as ARI1, ADH6, ADH7 and OYE3, as well as gene interactions involved in the biotransformation and inhibitor detoxification were direct driving force to reduce HMF damages in cells. Expressions of these genes were regulated by YAP1 and its closely related regulons. Second, a large number of PDR genes, mainly regulated by PDR1 and PDR3, were induced during the lag phase and the PDR gene family-centered functions, including specific and multiple functions involving cellular transport such as TPO1, TPO4, RSB1, PDR5, PDR15, YOR1, and SNQ2, promoted cellular adaptation and survival in order to cope with the inhibitor stress. Third, expressed genes involving degradation of damaged proteins and protein modifications such as SHP1 and SSA4, regulated by RPN4, HSF1 and other co-regulators, were necessary for yeast cells to survive and adapt the HMF stress. A deletion mutation strainΔrpn4 was unable to recover the growth in the presence of HMF. Complex gene interactions and regulatory networks as well as co-regulations exist in yeast adaptation and tolerance to the lignocellulose derived inhibitor HMF. Both induced and repressed genes involving diversified functional categories are accountable for adaptation and energy rebalancing in yeast to survive and adapt the HMF stress during the lag phase of growth. Transcription factor genes YAP1, PDR1, PDR3, RPN4 and HSF1 appeared to play key regulatory rules for global adaptation in the yeast S. cerevisiae.

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Transcriptome analyses of pdr5Dyor1D mutant in yeasts

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