Cellular stress response pathways often require transcription-based activation of gene expression to promote cellular adaptation. However, whether general mechanisms exist for stress-responsive gene down-regulation is less clear. A recently defined gene regulatory mechanism enables both up- and down-regulation of protein levels for distinct gene sets by the same transcription factor (TF) via coordinated induction of canonical mRNAs and long undecoded transcript isoforms (LUTIs). We analyzed deep, parallel gene expression datasets to determine whether this mechanism contributes to the conserved Hac1-driven branch of the unfolded protein response (UPRER). Indeed, we found Hac1-dependent protein down-regulation that accompanied the well-characterized up-regulation of ER-related proteins that typifies UPRER activation. Proteins down-regulated by Hac1-driven LUTIs include those with electron transport chain (ETC) function. Aerobic respiration also appears dampened during the UPRER, and abrogated ETC function improves the fitness of UPRER-activated cells, suggesting functional importance of LUTI regulation during the UPRER. We conclude that the UPRER involves large-scale proteome remodeling, mediated in part by Hac1-induced LUTIs, and that this mechanism enables coordination of up- and down-regulation of gene expression during this stress response. Overall design: Sequencing of mRNA molecules and ribosome footprints to identify regulated transcript isoform changes that result in apparent translational regulation. In short, two major experiments are included here, one for parallel mRNA-seq and ribosome profiling of cells with or without UPR induction by either DTT or Tm, with or without deletion of HAC1. The other experiment investigates the examines the same type of measurements for cells that are either WT or depleted for Hac1 and treated with DTT.