title: Quality control of nonstop membrane proteins at the ER membrane and in the cytosol.
abstract: Since messenger RNAs without a stop codon (nonstop mRNAs) for organelle-targeted proteins and their translation products (nonstop proteins) generate clogged translocon channels as well as stalled ribosomes, cells have mechanisms to degrade nonstop mRNAs and nonstop proteins and to clear the translocons (e.g. the Sec61 complex) by release of nonstop proteins into the organellar lumen. Here we followed the fate of nonstop endoplasmic reticulum (ER) membrane proteins with different membrane topologies in yeast to evaluate the importance of the Ltn1-dependent cytosolic degradation and the Dom34-dependent release of the nonstop membrane proteins. Ltn1-dependent degradation differed for membrane proteins with different topologies and its failure did not affect ER protein import or cell growth. On the other hand, failure in the Dom34-dependent release of the nascent polypeptide from the ribosome led to the block of the Sec61 channel and resultant inhibition of other protein import into the ER caused cell growth defects. Therefore, the nascent chain release from the translation apparatus is more instrumental in clearance of the clogged ER translocon channel and thus maintenance of normal cellular functions.
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Arakawa
authors.affiliation: Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan.|JST/CREST, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yunoki
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Research Center for Materials Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.|Department of Material and Biological Chemistry, Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.|Department of Biology, Faculty of Science, Niigata University, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Shuh-Ichi
authors.initials: S
authors.lastname: Nishikawa
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.|Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan.|JST/CREST, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Endo
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D010445:Peptide Elongation Factors / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport; D059748:Proteolysis; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry*; D000069816:SEC Translocation Channels / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C077247:HBS1 protein, S cerevisiae; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D010445:Peptide Elongation Factors; D012333:RNA, Messenger; D000069816:SEC Translocation Channels; D029701:Saccharomyces cerevisiae Proteins; C552998:Ltn1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; C112808:Dom34 protein, S cerevisiae; D004722:Endoribonucleases; D046988:Proteasome Endopeptidase Complex; D019204:GTP-Binding Proteins