Alternative splicing of PTC7 in Saccharomyces cerevisiae determines protein localization.
It is well established that higher eukaryotes use alternative splicing to increase proteome complexity. In contrast, Saccharomyces cerevisiae, a single-cell eukaryote, conducts predominantly regulated splicing through retention of nonfunctional introns. In this article we describe our discovery of a functional intron in the PTC7 (YHR076W) gene that can be alternatively spliced to create two mRNAs that code for distinct proteins. These two proteins localize to different cellular compartments and have distinct cellular roles. The protein translated from the spliced mRNA localizes to the mitochondria and its expression is carbon-source dependent. In comparison, the protein translated from the unspliced mRNA contains a transmembrane domain, localizes to the nuclear envelope, and mediates the toxic effects of Latrunculin A exposure. In conclusion, we identified a definitive example of functional alternative splicing in S. cerevisiae that confers a measurable fitness benefit.
Juneau
Kara
K
Stanford Genome Technology Center, Department of Biochemistry, Stanford University School of Medicine, 855 California Ave., Palo Alto, California 94304, USA. kjuneau@stanford.edu
Nislow
Corey
C
Davis
Ronald W
RW
D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology; D001483:Base Sequence; D001682:Biological Availability; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002244:Carbon / Q000493:pharmacokinetics; D025141:Drug Resistance, Fungal / Q000235:genetics; D047668:Inteins / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D053778:Thiazolidines / Q000494:pharmacology; D014018:Tissue Distribution / Q000235:genetics
D000935:Antifungal Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007527:Isoenzymes; D029701:Saccharomyces cerevisiae Proteins; D053778:Thiazolidines; D002244:Carbon; C433364:PTC7 protein, S cerevisiae; D054648:Protein Phosphatase 2; C037067:latrunculin A