The transcriptional co-activator ADA5 is required for HAC1 mRNA processingin vivo

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activat es signaling pathways to induce transcription of a number of genes encoding ER protein chaperones and-folding catalysts. In Saccharomyces cerevisiae t his transcriptional induction is mediated by an increase in the synthesis o f the transcription factor Hac1p, The transmembrane receptor Ire1p/Em1p con taining a Ser/Thr protein kinase and endoribonuclease activity transmits th e unfolded protein response (UPR) from the ER to the nucleus. Activation of Ire1p kinase induces its endoribonuclease activity to cleave unspliced HAC 1 mRNA and generate exon fragments that are subsequently ligated by tRNA li gase (RLG1). Whereas unspliced HAC1 mRNA is poorly translated, spliced HAC1 mRNA is efficiently translated. Subunits of the yeast transcriptional co-a ctivator complex SAGA also play a role in the UPR. Deletion of GCN5, ADA2, or ADA3 reduces, and deletion of ADA5 completely abolishes, the UPR, Althou gh HAC1 mRNA requires only Ire1p and Rlg1p in vitro, we demonstrate that AD A5 is required for the IRE1/RLG1-dependent splicing reaction of HAC1 mRNA i n vivo. In addition, Ada5p interacts with Tre1p. These results suggest that subcomponents of transcriptional co-activator complexes may be involved in RNA processing events.