Guanine nucleotide negatively regulates yeast inosine monophosphate dehydrogenase (IMPDH) mRNA synthesis by an unknown mechanism. IMPDH catalyzes the first dedicated step of GTP biosynthesis, and feedback control of its expression maintains the proper balance of purine nucleotides. Here we show that RNA polymerase II (Pol II) responds to GTP concentration. When GTP is sufficient, Pol II initiates transcription of the IMPDH gene (IMD2) at TATA box-proximal "G" sites, producing attenuated transcripts. When GTP is deficient, Pol II initiates at an "A" further downstream, circumventing the regulatory terminator to produce IMPDH mRNA. A major determinant for GTP concentration-dependent initiation at the upstream sites is the presence of guanine at the first and second positions of the transcript. Mutations in the Rpb1 subunit of Pol II and in TFIIB disrupt IMD2 regulation by altering start site selection. Thus, Pol II initiation can be regulated by the concentration of initiating nucleotide.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|