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doi:10.1534/genetics.106.057489
A more recent version of this article appeared on June 1, 2006.
REGULAR RESEARCH PAPERS |
Genomic analysis of the Opi- phenotype
Leandria C Hancock 1, Ryan P Behta 1 and John M Lopes 1*
1 Wayne State University
* To whom correspondence should be addressed. E-mail: jlopes{at}sun.science.wayne.edu.
Submitted on February 21, 2006
Revised on March 28, 2006
Accepted on 28 March 2006
Most of the phospholipid biosynthetic genes of Saccharomyces cerevisiae are coordinately regulated in response to inositol and choline. Inositol affects the intracellular levels of phosphatidic acid (PA). Opi1p is a repressor of the phospholipid biosynthetic genes and specifically binds PA in the endoplasmic reticulum. In the presence of inositol, PA levels decrease releasing Opi1p into the nucleus where it represses transcription. The opi1 mutant overproduces and excretes inositol (Opi- phenotype). To better understand the mechanism of Opi1p repression, the viable yeast deletion set was screened to identify Opi- mutants. In total, 89 Opi- mutants were identified of which 7 were previously known to have the Opi- phenotype. The Opi- mutant collection included genes with roles in phospholipid biosynthesis, transcription, protein processing/synthesis, and protein trafficking. Included in this set were all non-essential components of the NuA4 HAT complex and six proteins in the Rpd3p-Sin3p HDAC complex. It has previously been shown that defects in phosphatidylcholine synthesis (cho2 and opi3) yield the Opi- phenotype because of a build-up of PA. However, in this case the Opi- phenotype is conditional because PA can be shuttled through a salvage pathway (Kennedy pathway) by adding choline to the growth medium. Seven new mutants present in the Opi- collection (fun26, kex1, nup84, tps1, mrpl38, mrpl49, and opi10/yol032w) were also suppressed by choline suggesting that these affect PC synthesis. Regulation in response to inositol is also coordinated with the Unfolded Protein Response (UPR). Consistent with this, several Opi- mutants were found affect the UPR (yhi9, ede1, and vps74).
Key Words: INO1, Opi-, Phospholipid, Transcriptional regulation, Unfolded protein response