Yeast unfolded protein response pathway regulates expression of genes for anti-oxidative stress and for cell surface proteins

The unfolded protein response (UPR) is a cellular protective event against endoplasmic reticulum (ER) stress. In the yeast UPR signaling pathway, the ER-located transmembrane protein Ire1 promotes splicing of the HAC1 premRNA (HAC1(u)) to produce the translatable transcription factor mRNA (HAC1(i)). We generated a HAC1(i) gene-bearing strain, in which the UPR pathway was constitutively activated, and compared its gene expression profile with that of a Delta ire1 HAC1(u) strain using cDNA microarray technology. Comparison of the gene expression profile was also performed between non-stressed wild-type cells and those exposed to ER stress. Genes for which the expression level was significantly changed in both of these experiments were categorized as targets of the Ire1-HAC1 signaling pathway. This analysis revealed that in addition to the previously known UPR targets, some anti-oxidative stress genes were up-regulated by the Ire1-HAC1 pathway, possibly in order to reduce reactive oxygen species produced during the cellular response to ER stress. Moreover, we categorized 15 genes as those down-regulated by the UPR, most of which seem to encode cell surface or extracellular proteins. This UPR-mediated gene repression may alleviate the load of client proteins targeted to the ER.