title: A novel role for protein kinase Kin2 in regulating HAC1 mRNA translocation, splicing, and translation.
abstract: A signaling network called the unfolded protein response (UPR) resolves the protein-folding defects in the endoplasmic reticulum (ER) from yeasts to humans. In the yeast Saccharomyces cerevisiae, the UPR activation involves (i) aggregation of the ER-resident kinase/RNase Ire1 to form an Ire1 focus, (ii) targeting HAC1 pre-mRNA toward the Ire1 focus that cleaves out an inhibitory intron from the mRNA, and (iii) translation of Hac1 protein from the spliced mRNA. Targeting HAC1 mRNA to the Ire1 focus requires a cis-acting bipartite element (3'BE) located at the 3' untranslated leader. Here, we report that the 3'BE plays an additional role in promoting translation from the spliced mRNA. We also report that a high dose of either of two paralogue kinases, Kin1 and Kin2, overcomes the defective UPR caused by a mutation in the 3'BE. These results define a novel role for Kin kinases in the UPR beyond their role in cell polarity and exocytosis. Consistently, targeting, splicing, and translation of HAC1 mRNA are substantially reduced in the kin1Δ kin2Δ strain. Furthermore, we show that Kin2 kinase domain itself is sufficient to activate the UPR, suggesting that Kin2 initiates a signaling cascade to ensure an optimum UPR.
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Anshu
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
authors.forename: M Amin-Ul
authors.initials: MA
authors.lastname: Mannan
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chakraborty
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Chakrabarti
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA deym@uwm.edu.
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Dey
mesh_terms: D020413:3' Untranslated Regions; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005089:Exocytosis; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D018613:Microscopy, Confocal; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D020413:3' Untranslated Regions; D050976:Basic-Leucine Zipper Transcription Factors; C091341:HAC1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; C082863:IRE1 protein, S cerevisiae; C490209:KIN1 protein, S cerevisiae; C087572:KIN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases