tRNA ligase is required for regulated mRNA splicing in the unfolded protein response.
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers an intracellular signaling pathway, the unfolded protein response (UPR), that leads to increased transcription of genes encoding ER-resident proteins. Transcriptional activation is mediated by a dedicated transcription factor, Hac1p, whose activity is controlled by regulated splicing of its mRNA. We have identified a mutation in tRNA ligase that disrupts the UPR in the yeast Saccharomyces cerevisiae. In this mutant, splicing of HAC1 mRNA, but not tRNA, is blocked. In contrast, HAC1 mRNA splicing is not impaired in cells that are blocked in spliceosome-mediated mRNA splicing. Furthermore, the splice junctions of HAC1 mRNA do not conform to the consensus sequences of other yeast pre-mRNAs. Our results suggest that the regulated splicing of HAC1 mRNA occurs by a novel pathway, involving tRNA ligase and bypassing the spliceosome.
Department of Biochemistry and Biophysics, University of California School of Medicine, San Francisco 94143-0448, USA.
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Sidrauski
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Cox
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Walter
D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D016384:Consensus Sequence; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D017510:Protein Folding; D011130:RNA Ligase (ATP) / Q000502:physiology*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017381:Spliceosomes / Q000502:physiology; D014157:Transcription Factors
D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins; C091341:HAC1 protein, S cerevisiae; D018840:HSP70 Heat-Shock Proteins; C060153:KAR2 protein, yeast; D012322:RNA Precursors; D012331:RNA, Fungal; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011130:RNA Ligase (ATP)