title: Dissection of Dom34-Hbs1 reveals independent functions in two RNA quality control pathways.
abstract: Eukaryotic cells have several quality control pathways that rely on translation to detect and degrade defective RNAs. Dom34 and Hbs1 are two proteins that are related to translation termination factors and are involved in no-go decay (NGD) and nonfunctional 18S ribosomal RNA (rRNA) decay (18S NRD) pathways that eliminate RNAs that cause strong ribosomal stalls. Here we present the structure of Hbs1 with and without GDP and a low-resolution model of the Dom34-Hbs1 complex. This complex mimics complexes of the elongation factor and transfer RNA or of the translation termination factors eRF1 and eRF3, supporting the idea that it binds to the ribosomal A-site. We show that nucleotide binding by Hbs1 is essential for NGD and 18S NRD. Mutations in Hbs1 that disrupted the interaction between Dom34 and Hbs1 strongly impaired NGD but had almost no effect on 18S NRD. Hence, NGD and 18S NRD could be genetically uncoupled, suggesting that mRNA and rRNA in a stalled translation complex may not always be degraded simultaneously.
authors.affiliation: Equipe Labellisée La Ligue, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGMBC), Illkirch, France.
authors.forename: Antonia M G
authors.initials: AM
authors.lastname: van den Elzen
authors.forename: Julien
authors.initials: J
authors.lastname: Henri
authors.forename: Noureddine
authors.initials: N
authors.lastname: Lazar
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Gas
authors.forename: Dominique
authors.initials: D
authors.lastname: Durand
authors.forename: François
authors.initials: F
authors.lastname: Lacroute
authors.forename: Magali
authors.initials: M
authors.lastname: Nicaise
authors.forename: Herman
authors.initials: H
authors.lastname: van Tilbeurgh
authors.forename: Bertrand
authors.initials: B
authors.lastname: Séraphin
authors.forename: Marc
authors.initials: M
authors.lastname: Graille
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D008958:Models, Molecular; D009154:Mutation; D010445:Peptide Elongation Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D020871:RNA Stability; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D018797:Cell Cycle Proteins; C077247:HBS1 protein, S cerevisiae; D018840:HSP70 Heat-Shock Proteins; D010445:Peptide Elongation Factors; D012337:RNA, Ribosomal, 18S; D029701:Saccharomyces cerevisiae Proteins; C112808:Dom34 protein, S cerevisiae; D004722:Endoribonucleases; D019204:GTP-Binding Proteins