Stress response in the yeast Saccharomyces cerevisiae involves the detection of adverse conditions (high or low osmolarity, nutrient limitation, ethanol exposure, increased level of oxidant reagents, variations in pH, etc.), activation of signal transduction pathways, and transcriptional and posttranscriptional regulation, resulting in the accumulation of protective agents and repairing activities . All these mechanisms are intended to allow yeast cells to adapt to environmental changes.
Under several different stress conditions, S. cerevisiae displays a common response, the so-called Environmental Stress Response (ESR), characterized by changes in the expression of approximately 900 genes . Most of these genes contain the AGGG consensus sequence in their promoter , which is recognized by transcription factors Msn2p and Msn4p . The activity of these factors is regulated by two pathways that control cell growth: Protein Kinase A (PKA, ) and Target of Rapamycin (TOR, ).
Besides this general response, yeast cells display specific mechanisms to resist particular adverse conditions. In the case of hyperosmotic stress, produced by a high concentration of salt, sorbitol, glucose or of any other osmolyte, the response is mediated by the High Osmolarity Glycerol (HOG) pathway. High osmolarity is detected by osmosensors located in the membrane, that activate MAP quinases which, finally, permit the phosphorylation of MAPK Hog1p, which results in its translocation to the nucleus. Once inside this compartment, Hog1p activates several transcription factors (Hot1p, Msn1p, Smp1p, Gcn4p, Skn7p, Sko1p, Msn2p and Msn4p) [1, 7, 8]. These factors determine an induction in the expression of about 10% of the yeast genes under conditions of stress caused by high salt or sorbitol concentrations [2, 9–12]. One of the consequences of these changes in gene expression is an increase in the intracellular concentration of glycerol, the osmolyte that yeast cells produce to counteract hyperosmotic stress.
One of the conditions of hyperosmotic stress that can affect yeast cells in particular environments (for instance, during the production of alcoholic beverages) is that produced by sugar concentrations of 20% (w/v) or even higher. Several transcriptomic analyses have been carried out to understand the particularities of the response to this form of stress [13–15]. All these studies have indicated that three groups of genes display higher expression levels under these conditions: i) genes involved in glycerol metabolism, ii) genes participating in response to chemical stimulus, and iii) several genes of unknown function. One of them, YHR087W, is induced approximately 5 times under 20% glucose and encodes for a protein of 111 amino acids (12 kDa). The expression of this gene also increases under other hyperosmotic stress conditions (salt and sorbitol) and in response to other adverse conditions such as heat shock, oxidative damage produced by H2O2 or diamide, ethanol, acid or basic pHs and the stationary phase [2, 11, 16]. The increase in the YHR087W mRNA levels under 20% glucose is also followed by higher content of the corresponding protein .
Some of the data obtained in recent years have demonstrated the relevance of the YHR087W gene expression in the response to high sugar concentrations. On the one hand, its overexpression in wine yeast strains results in an improved stress response and fermentative behavior . Besides, strains with a high resistance to osmotic stress show higher mRNA levels corresponding to this gene . Finally in laboratory strains, its disruption results in growth delay, lower viability and reduced glucose consumption under 25% and 30% glucose concentrations .
From the structural point of view, Yhr087wp presents a strong homology with the protein family related with human SBDS . SBDS is the human protein whose mutation provokes the Shwachman-Bodian-Diamond syndrome, a rare autosomal recessive disorder with clinical features, including haematological dysfunction, pankreatic exocrine insufficiency and skeletal abnormalities, as well as a significant predisposition to the development of myelodysplasia and leukemia [19–21]. The yeast orthologue of SBDS is Sdo1p . Yhr087wp contains the same structural elements as Sdo1p in the N-terminus region and, according to sequence analyses [18, 23], they are distant homologues.
Sdo1p binds RNA, interacts with nuclear rRNA-processing factors , and is involved in the maturation of the ribosomal 60 S subunit required for the translational activation of ribosomes . There is a report describing an aberrant regulation of Btn1p in the absence of Sdo1p, which suggests that portions of the ribosome maturation pathways survey the vacuolar function, presumably as a means to adjust protein levels for optimal cellular homeostasis . Due to the structural relationship between Yhr087wp and Sdo1p, it has been proposed that the role of that protein in yeast cells would be associated in some way with the RNA metabolism . Actually, synthetic lethality has been described between yhr087w and the mutants in genes encoding proteins involved in RNA processing and transport, translation and posttranslational processes ( nat3 –acetylation of ribosomal proteins-, nsr1 -synthesis of rRNA 18 S and its precursor 20 S-, air1 –nuclear RNA processing-, npl3 and yra2p -mRNA export ).
However, the data found by other authors suggest that Yhr087wp could be involved in other cellular processes. The YHR087W gene has also been named RTC3 (from Restriction of Telomere Capping) because its null mutant suppresses the phenotype of termosensitive mutant cdc13-1. In this mutant, at the non-permissive temperature, telomeric DNA is degraded and cell cycle progression is impaired. On the other hand, Costanzo et al.  described genetic interactions between YHR087W and several genes encoding proteins related with transcription and its control, such as Nut1p (a component of the RNA polymerase II mediator complex), Set3p (a member of a histone desacetylase complex), Npl3p (RNA polymerase II transcription elongation), Cna1p (a component of calcineurin) or Bcy1p (a regulatory subunit of the PKA). Finally, the results of a recent proteomic comparison made in our laboratory between deletion mutant Δyhr087w and its corresponding wild type strain  under 20% glucose showed lower levels of two proteins involved in protein folding (Hsp104p and Hsp78p) in the mutant strain, which appeared as an overrepresented category. In this sense, genetic interactions have been described between yhr087w and hsp82.
In this work we carry out several experiments in order to gain more insights into the role of Yhr087wp in yeast cells. The data obtained confirms once more the relationship between this protein and the stress response, provides new information about its transcriptional regulation, and points to a role in translation under adverse growth conditions.