Yeast Frameshift Suppressor Mutations in the Genes Coding for Transcription Factor Mbf1p and Ribosomal Protein S3: Evidence for Autoregulation of S3 Synthesis

• Published in: Genetics (Austin) 2001-03, Vol.157 (3), p.1141-1158
• Main Authors: Hendrick, James L, Wilson, Patricia G, Edelman, Irving I, Sandbaken, Mark G, Ursic, Doris, Culbertson, Michael R
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; Alleles; Copper - pharmacology; Databases, Factual; Dose-Response Relationship, Drug; Frameshift Mutation; Gene Dosage; Genes; Genes, Fungal; Genetics; Models, Genetic; Mutation; Phenotype; Plasmids - genetics; Plasmids - metabolism; Promoter Regions, Genetic; Ribosomal Proteins - biosynthesis; Ribosomal Proteins - genetics; RNA, Messenger - metabolism; Saccharomyces cerevisiae Proteins; Suppression, Genetic; Time Factors; Trans-Activators - genetics; Transcription Factors; Transcription, Genetic; Transformation, Genetic; Yeast
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1093/genetics/157.3.1141

The SUF13 and SUF14 genes were identified among extragenic suppressors of +1 frameshift mutations. SUF13 is synonymous with MBF1, a single-copy nonessential gene coding for a POLII transcription factor. The suf13-1 mutation is a two-nucleotide deletion in the SUF13/MBF1 coding region. A suf13::TRP1 null mutant suppresses +1 frameshift mutations, indicating that suppression is caused by loss of SUF13 function. The suf13-1 suppressor alters sensitivity to aminoglycoside antibiotics and reduces the accumulation of his4-713 mRNA, suggesting that suppression is mediated at the translational level. The SUF14 gene is synonymous with RPS3, a single-copy essential gene that codes for the ribosomal protein S3. The suf14-1 mutation is a missense substitution in the coding region. Increased expression of S3 limits the accumulation of SUF14 mRNA, suggesting that expression is autoregulated. A frameshift mutation in SUF14 that prevents full-length translation eliminated regulation, indicating that S3 is required for regulation. Using CUP1-SUF14 and SUF14-lacZ fusions, run-on transcription assays, and estimates of mRNA half-life, our results show that transcription plays a minor role if any in regulation and that the 5'-UTR is necessary but not sufficient for regulation. A change in mRNA decay rate may be the primary mechanism for regulation.