Abstract
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates signaling pathways to induce transcription of a number of genes encoding ER protein chaperones and-folding catalysts. In Saccharomyces cerevisiae this transcriptional induction is mediated by an increase in the synthesis of the transcription factor Hac1p. The transmembrane receptor Ire1p/Ern1p containing a Ser/Thr protein kinase and endoribonuclease activity transmits the unfolded protein response (UPR) from the ER to the nucleus. Activation of Ire1p kinase induces its endoribonuclease activity to cleave unspliced HAC1 mRNA and generate exon fragments that are subsequently ligated by tRNA ligase (RLG1). Whereas unspliced HAC1 mRNA is poorly translated, spliced HAC1 mRNA is efficiently translated. Subunits of the yeast transcriptional co-activator complex SAGA also play a role in the UPR. Deletion of GCN5, ADA2, or ADA3 reduces, and deletion of ADA5 completely abolishes, the UPR. Although HAC1 mRNA requires only Ire1p and Rlg1p in vitro, we demonstrate that ADA5 is required for the IRE1/RLG1-dependent splicing reaction of HAC1 mRNA in vivo. In addition, Ada5p interacts with Ire1p. These results suggest that subcomponents of transcriptional co-activator complexes may be involved in RNA processing events.
Highlights
The lumen of the endoplasmic reticulum (ER)1 is a highly specialized compartment in eukaryotic cells
Transcription of HAC1 and/or IRE1 Is Not Attenuated in ⌬ada5 Cells—GCN5, ADA2, ADA3, and ADA5 are required for the maximal transcriptional induction of genes encoding ER resident chaperones including KAR2/BiP in response to protein misfolding in the ER [16]
The SAGA complex is not required for the heat-mediated transcriptional activation of KAR2 [16], suggesting that these co-activators play a specific role in the unfolded protein response (UPR) as opposed to global transcriptional induction
Summary
The lumen of the endoplasmic reticulum (ER)1 is a highly specialized compartment in eukaryotic cells. In the budding yeast Saccharomyces cerevisiae, genes that are transcriptionally activated in response to unfolded proteins in the ER contain a 22-base pair cis-acting promoter element, termed the UPRE, that is necessary and sufficient to mediate the transcriptional induction [2]. HAC1 mRNA splicing allows efficient translation of Hac1p and subsequent transcriptional activation of genes regulated by the UPR.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
