Disease relevance of OLE1

• To define the possible roles of each of these genes on hypoxia-induced OLE1 expression, we examined OLE1 expression under normoxia, hypoxia, and cobalt treatment conditions in Deltamga2 or Deltaspt23 deletion strains [1].
• Mutation of host delta9 fatty acid desaturase inhibits brome mosaic virus RNA replication between template recognition and RNA synthesis [2].
• Recent findings on the structure and expression of different types of fatty acid desaturase in cyanobacteria, plants and animals are reviewed in this article [3].

High impact information on OLE1

• The OLE pathway of yeast regulates the level of the ER-bound enzyme Delta9-fatty acid desaturase OLE1, thereby controlling membrane fluidity [4].
• We found that CDC48(UFD1/NPL4) plays a second role in the OLE pathway by mediating ERAD of OLE1 [5].
• Here we report that the OLE1 protein itself is naturally short-lived and is degraded by ubiquitin/proteasome-dependent ER-associated degradation (ERAD) [5].
• In addition, transition metals (Co and Ni) induce the expression of OLE1 and CYC7 in a concentration-dependent manner under aerobic conditions [6].
• Fluorescence anisotropy of mitochondrial membranes of completed strains corresponded to the different activity of the Ole1 promoter used [7].

Biological context of OLE1

• An analysis of mutants that are defective in mRNA degradation indicate that the Mga2p-requiring control mechanism that regulates the fatty acid-mediated instability of the OLE1 transcript acts by activating exosomal 3' --> 5'-exonuclease degradation activity [8].
• A deletion analysis of OLE1 promoter::lacZ fusion reporter genes identified a 111-base pair (bp) fatty acid-regulated (FAR) region approximately 580 bp upstream of the start codon that is essential for transcription activation and unsaturated fatty acid repression [9].
• The fatty acid repression of transcription under those conditions is attenuated by Spt23Deltatm, however, suggesting that the two proteins may interact to modulate OLE1 gene expression [10].
• Regulatory elements that control transcription activation and unsaturated fatty acid-mediated repression of the Saccharomyces cerevisiae OLE1 gene [9].
• By EMS mutagenesis, we isolated three classes of mutants, pfo1, pfo2 and pfo3 positive regulatory factor for OLE1) mutants, which show decreased rAPase activity under derepression conditions (absence of oleic acid) [11].

Anatomical context of OLE1

• Expression of OLE1 is activated by N-terminal proteolytic fragments of two homologous endoplasmic reticulum membrane proteins, Spt23p and Mga2p [10].
• The products of Ole1p catalysis, oleic acid and palmitoleic acid, suppress mga2Delta spt23-ts and mga2Delta spt23Delta lethality and restore normal nuclear membrane morphology [12].
• Therefore, it is considered that ATF1 and OLE1 transcription are regulated in response to cell membrane fluidity [13].
• The discovery of CmFAD9 indicates the existence of a novel type of plant delta-9 fatty acid desaturase that may function in the endoplasmic reticulum, but not in the plastid [14].

Associations of OLE1 with chemical compounds

• Mga2p of Saccharomyces cerevisiae is an endoplasmic reticulum (ER)-localized transcription factor that plays an overlapping role with homologous Spt23p in upregulating expression of OLE1, a gene required for the synthesis of essential oleic acid [15].
• Expressed alone, Mga2p induces high levels of OLE1 transcription in cells exposed to cobalt or grown in glycerol-containing medium [10].
• We have found that carbon monoxide (CO) completely blocks the anoxia-induced expression of two hypoxic genes, OLE1 and CYC7, partially blocks the induction of a third gene, COX5b, and has no effect on the expression of other hypoxic or aerobic genes [6].
• Inhibition of translation, by the addition of cycloheximide, slows the nucleolytic degradation of the OLE1 mRNA and blocks the unsaturated fatty acid-triggered reduction in its half-life [16].
• Yeast adaptation to 2,4-dichlorophenoxyacetic acid involves increased membrane fatty acid saturation degree and decreased OLE1 transcription [17].

Regulatory relationships of OLE1

• Spt23p expressed alone activates OLE1 transcription to levels similar to those in wild type cells [10].
• These results suggested that ATF1 transcription was co-regulated by the same mechanism as the OLE1 gene and that unsaturated fatty acids and oxygen repressed the ATF1 transcript by a different regulation pathway [13].
• A similar chimera under GAL1 control that replaces the OLE1 mRNA 5'-untranslated region with GAL1 sequences is not regulated by unsaturated fatty acids [16].
• It exhibited Delta12 fatty acid desaturase activity when expressed in S. cerevisiae under the control of ADH1 promoter and produced endogenous linoleic acid [18].

Other interactions of OLE1

• Mga2p appears to have two distinct functions with respect to the OLE1 mRNA stability: a stabilizing effect in cells grown in fatty acid-free medium and a destabilizing function in cells that are exposed to unsaturated fatty acids [8].
• An analysis of spt23Delta and mga2Delta strains shows that Spt23p and Mga2p differentially activate and regulate OLE1 transcription [10].
• These functions are independent of OLE1 transcription and can confer basal and regulated stability on OLE1 mRNAs that are produced under the control of the unrelated GAL1 promoter [8].
• Two fatty acid activation genes, FAA1 and FAA4, were found to be essential for unsaturated fatty acid repression of OLE1 through the FAR sequences [9].
• In addition, four other classes of mutants, nfo1, nfo2, nfo3 and nfo4 (negative factor for OLE1) mutants that have mutations causing strong expression of the OLE1p-PHO5 fusion gene under repression conditions (presence of oleic acid), were isolated [11].

Analytical, diagnostic and therapeutic context of OLE1

• Northern blot analysis, however, showed that this gene is expressed at much lower levels ( approximately 150-fold) than the OLE1 gene, suggesting that it might act on a smaller subset of fatty acids [19].
• Sequence analysis of Fah1p reveals other similarities to Ole1p [19].
• Molecular cloning and characterization of the Delta9 fatty acid desaturase gene and its promoter region from Saccharomyces kluyveri [20].
• A delta-9 fatty acid desaturase gene, homologous to animal and fungal acyl-coenzyme A (CoA) desaturases, was isolated from the red alga Cyanidioschyzon merolae using a degenerate PCR strategy [14].

References