title: Translational pausing ensures membrane targeting and cytoplasmic splicing of XBP1u mRNA.
abstract: Upon endoplasmic reticulum (ER) stress, an endoribonuclease, inositol-requiring enzyme-1α, splices the precursor unspliced form of X-box-binding protein 1 messenger RNA (XBP1u mRNA) on the ER membrane to yield an active transcription factor (XBP1s), leading to the alleviation of the stress. The nascent peptide encoded by XBP1u mRNA drags the mRNA-ribosome-nascent chain (R-RNC) complex to the membrane for efficient cytoplasmic splicing. We found that translation of the XBP1u mRNA was briefly paused to stabilize the R-RNC complex. Mutational analysis of XBP1u revealed an evolutionarily conserved peptide module at the carboxyl terminus that was responsible for the translational pausing and was required for the efficient targeting and splicing of the XBP1u mRNA. Thus, translational pausing may be used for unexpectedly diverse cellular processes in mammalian cells.
authors.affiliation: Laboratory of Molecular and Cell Genetics, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Yanagitani
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kimata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kadokura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
mesh_terms: D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007425:Intracellular Membranes / Q000378:metabolism; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D012270:Ribosomes / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases