Dataset Information

Posttranscriptional Regulation of Gcr1 Expression and Activity Is Crucial for Metabolic Adjustment in Response to Glucose Availability.

ABSTRACT: The transcription factor Gcr1 controls expression of over 75% of the genes in actively growing yeast. Yet despite its widespread effects, regulation of Gcr1 itself remains poorly understood. Here, we show that posttranscriptional Gcr1 regulation is nutrient dependent. Moreover, GCR1 RNA contains a long, highly conserved intron, which allows the cell to generate multiple RNA and protein isoforms whose levels change upon glucose depletion. Intriguingly, an isoform generated by intron retention is exported from the nucleus, and its translation is initiated from a conserved, intronic translation start site. Expression of gene products from both the spliced and unspliced RNAs is essential, as cells expressing only one isoform cannot adjust their metabolic program in response to environmental changes. Finally, we show that the Gcr1 proteins form dimers, providing an elegant mechanism by which this one gene, through its regulation, can perform the repertoire of transcriptional activities necessary for fine-tuned environmental response.

SUBMITTER: Hossain MA

PROVIDER: S-EPMC5117908 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Posttranscriptional Regulation of Gcr1 Expression and Activity Is Crucial for Metabolic Adjustment in Response to Glucose Availability.

Hossain Munshi Azad MA Claggett Julia M JM Edwards Samantha R SR Shi Aishan A Pennebaker Sara L SL Cheng Melodyanne Y MY Hasty Jeff J Johnson Tracy L TL

Molecular cell 20160501 3

The transcription factor Gcr1 controls expression of over 75% of the genes in actively growing yeast. Yet despite its widespread effects, regulation of Gcr1 itself remains poorly understood. Here, we show that posttranscriptional Gcr1 regulation is nutrient dependent. Moreover, GCR1 RNA contains a long, highly conserved intron, which allows the cell to generate multiple RNA and protein isoforms whose levels change upon glucose depletion. Intriguingly, an isoform generated by intron retention is ...[more]

PMID: 27153533

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Project description:This SuperSeries is composed of the following subset Series: GSE3205: Homeostatic Adjustment and Metabolic Remodeling in Glucose-limited Yeast Cultures Time Course 1 GSE3206: Homeostatic Adjustment and Metabolic Remodeling in Glucose-limited Yeast Cultures Time Course 2 Abstract: We studied the physiological response to glucose limitation in batch and steady-state (chemostat) cultures of Saccharomyces cerevisiae by following global patterns of gene expression. Glucose-limited batch cultures of yeast go through two sequential exponential growth phases, beginning with a largely fermentative phase, followed by an essentially completely aerobic use of residual glucose and evolved ethanol. Judging from the patterns of gene expression, the state of the cells growing at steady state in glucose-limited chemostats corresponds most closely with the state of cells in batch cultures just before they undergo this "diauxic shift." Essentially the same pattern was found between chemostats having a fivefold difference in steady-state growth rate (the lower rate approximating that of the second phase respiratory growth rate in batch cultures). Although in both cases the cells in the chemostat consumed most of the glucose, in neither case did they seem to be metabolizing it primarily through respiration. Although there was some indication of a modest oxidative stress response, the chemostat cultures did not exhibit the massive environmental stress response associated with starvation that also is observed, at least in part, during the diauxic shift in batch cultures. We conclude that despite the theoretical possibility of a switch to fully aerobic metabolism of glucose in the chemostat under conditions of glucose scarcity, homeostatic mechanisms are able to carry out metabolic adjustment as if fermentation of the glucose is the preferred option until the glucose is entirely depleted. These results suggest that some aspect of actual starvation, possibly a component of the stress response, may be required for triggering the metabolic remodeling associated with the diauxic shift. Refer to individual Series

Project description:Time course of batch growth. Reference (channel 1) was a culture grown in MD medium with 2.4 g/L glucose, with 5 slpm air-flow, stirring at 400 rpm and a constant 300C temperature, dilution 0.25 volumes/hour. The experimental (channel 2) time course samples were grown in batch for the indicated time. The "Low-D chemostat vs. High-D chemostat" hybridization's channel 2 sample was grown in a chemostat, with a dilution rate of 0.05 volumes/hour; it is most similar to the time course samples taken between 8 and 9 hours. Groups of assays that are related as part of a time series. FactorCategory: Elapsed Time; name: Elapsed Time; Measurement: time(absolute) 0 h; name: 45181_Elapsed Time; Measurement: time(absolute) 8.5 h; name: 38150_Elapsed Time; Measurement: time(absolute) 8.75 h; name: 38151_Elapsed Time; Measurement: time(absolute) 9 h; name: 38152_Elapsed Time; Measurement: time(absolute) 9.25 h; name: 38153_Elapsed Time; Measurement: time(absolute) 7.25 h; name: 38145_Elapsed Time; Measurement: time(absolute) 9.5 h; name: 38154_Elapsed Time; Measurement: time(absolute) 7.5 h; name: 38146_Elapsed Time; Measurement: time(absolute) 9.75 h; name: 38155_Elapsed Time; Measurement: time(absolute) 7.75 h; name: 38147_Elapsed Time; Measurement: time(absolute) 10 h; name: 38156_Elapsed Time; Measurement: time(absolute) 8 h; name: 38148_Elapsed Time; Measurement: time(absolute) 8.25 h; name: 38149_Elapsed Time FactorCategory: Growth Condition; name: Growth Condition; Growth Condition: chemostat dilution control; name: 45181_Growth Condition; Growth Condition: batch; name: 38150_Growth Condition; Growth Condition: batch; name: 38151_Growth Condition; Growth Condition: batch; name: 38152_Growth Condition; Growth Condition: batch; name: 38153_Growth Condition; Growth Condition: batch; name: 38145_Growth Condition; Growth Condition: batch; name: 38154_Growth Condition; Growth Condition: batch; name: 38146_Growth Condition; Growth Condition: batch; name: 38155_Growth Condition; Growth Condition: batch; name: 38147_Growth Condition; Growth Condition: batch; name: 38156_Growth Condition; Growth Condition: batch; name: 38148_Growth Condition; Growth Condition: batch; name: 38149_Growth Condition Computed

Dataset Information

Posttranscriptional Regulation of Gcr1 Expression and Activity Is Crucial for Metabolic Adjustment in Response to Glucose Availability.

Publications

Posttranscriptional Regulation of Gcr1 Expression and Activity Is Crucial for Metabolic Adjustment in Response to Glucose Availability.

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