title: Functional analysis of the mammalian RNA ligase for IRE1 in the unfolded protein response.
abstract: The unfolded protein response (UPR) is a conserved signalling pathway activated on the accumulation of unfolded proteins within the endoplasmic reticulum (ER), termed ER stress. Upon ER stress,HAC1/XBP1undergoes exon/intron-specific excision by inositol requiring enzyme 1 (IRE1) to remove an intron and liberate the 5' and 3' exons. In yeast, the 5' and 3'HAC1exons are subsequently ligated by tRNA ligase (Rlg1p), whereasXBP1ligation in mammalian cells is catalysed by a recently identified ligase, RtcB. In the present study, RNA ligase activity of the human RtcB (hRtcB) involved in the unconventional splicing ofXBP1/HAC1mRNA was explored in anrlg1-100mutant yeast strain. Distinct fromEscherichia coliRtcB and Rlg1p, expression of hRtcB alone inefficiently complementedHAC1/XBP1splicing and the hRtcB cofactor (archease) was required to promote enzymatic activity of hRtcB to catalyse RNA ligation.
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand.|Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, U.S.A.
authors.forename: Juthakorn
authors.initials: J
authors.lastname: Poothong
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand witoon.mu@gmail.com rkaufman@sbpdiscovery.org.
authors.forename: Witoon
authors.initials: W
authors.lastname: Tirasophon
authors.affiliation: Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, U.S.A. witoon.mu@gmail.com rkaufman@sbpdiscovery.org.
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology; D004926:Escherichia coli / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008025:Ligases / Q000378:metabolism*; D008322:Mammals / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D056811:Unfolded Protein Response / Q000235:genetics / Q000502:physiology*; D000071717:X-Box Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C091341:HAC1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000071717:X-Box Binding Protein 1; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D008025:Ligases
keywords: Rlg1p; archease; human IRE1α/XBP1; human RtcB; rlg1-100