title: The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells.
abstract: In yeast, aberrant mRNAs lacking in-frame termination codons are recognized and degraded by the non-stop decay (NSD) pathway. The recognition of non-stop mRNAs involves a member of the eRF3 family of GTP-binding proteins, Ski7. Ski7 is thought to bind the ribosome stalled at the 3'-end of the mRNA poly(A) tail and recruit the exosome to degrade the aberrant message. However, Ski7 is not found in mammalian cells, and even the presence of the NSD mechanism itself has remained enigmatic. Here, we show that unstable non-stop mRNA is degraded in a translation-dependent manner in mammalian cells. The decay requires another eRF3 family member (Hbs1), its binding partner Dom34, and components of the exosome-Ski complex (Ski2/Mtr4 and Dis3). Hbs1-Dom34 binds to form a complex with the exosome-Ski complex. Also, the elimination of aberrant proteins produced from non-stop transcripts requires the RING finger protein listerin. These findings demonstrate that the NSD mechanism exists in mammalian cells and involves Hbs1, Dom34, and the exosome-Ski complex.
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
authors.forename: Syuhei
authors.initials: S
authors.lastname: Saito
authors.forename: Nao
authors.initials: N
authors.lastname: Hosoda
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hoshino
mesh_terms: D004720:Endonucleases; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors / Q000502:physiology*; D011485:Protein Binding; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D004720:Endonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C550527:pelo protein, human; C551543:DIS3 protein, human; D019204:GTP-Binding Proteins; C000628258:HBS1L protein, human
keywords: Exosomes; Hbs1; Non-stop Decay; RNA Turnover; Ribosomes; Translation Release Factors; eRF3; mRNA Decay