title: 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.
authors.affiliation: Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Munshi Azad
authors.initials: MA
authors.lastname: Hossain
authors.affiliation: Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Claggett
authors.affiliation: Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Edwards
authors.affiliation: Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Aishan
authors.initials: A
authors.lastname: Shi
authors.affiliation: Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pennebaker
authors.affiliation: Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Melodyanne Y
authors.initials: MY
authors.lastname: Cheng
authors.affiliation: Molecular Biology Section, Division of Biological Sciences, San Diego Center for Systems Biology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Hasty
authors.affiliation: Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: tljohnson@ucla.edu.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Johnson
mesh_terms: D000222:Adaptation, Physiological; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005091:Exons; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D005947:Glucose / Q000172:deficiency / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics*; D007438:Introns; D009154:Mutation; D010641:Phenotype; D020033:Protein Isoforms; D055503:Protein Multimerization; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C076227:GCR1 protein, S cerevisiae; D020033:Protein Isoforms; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005947:Glucose