title: The transcriptional co-activator ADA5 is required for HAC1 mRNA processing in vivo.
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.
authors.affiliation: Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0650, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Welihinda
authors.forename: W
authors.initials: W
authors.lastname: Tirasophon
authors.forename: R J
authors.initials: RJ
authors.lastname: Kaufman
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D017510:Protein Folding; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C091341:HAC1 protein, S cerevisiae; D012333:RNA, Messenger; D012097:Repressor Proteins; C099690:SPT20 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors