title: The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation.
abstract: Protein quality control mechanisms eliminate defective polypeptides to ensure proteostasis and to avoid the toxicity of protein aggregates. In eukaryotes, the ribosome-bound quality control (RQC) complex detects aberrant nascent peptides that remain stalled in 60S ribosomal particles due to a dysfunction in translation termination. The RQC complex polyubiquitylates aberrant polypeptides and recruits a Cdc48 hexamer to extract them from 60S particles in order to escort them to the proteasome for degradation. Whereas the steps from stalled 60S recognition to aberrant peptide polyubiquitylation by the RQC complex have been described, the mechanism leading to proteasomal degradation of these defective translation products remains unknown. We show here that the RQC complex also exists as a ribosome-unbound complex during the escort of aberrant peptides to the proteasome. In addition, we identify a new partner of this light version of the RQC complex, the E3 ubiquitin ligase Tom1. Tom1 interacts with aberrant nascent peptides and is essential to limit their accumulation and aggregation in the absence of Rqc1; however, its E3 ubiquitin ligase activity is not required. Taken together, these results reveal new roles for Tom1 in protein quality control, aggregate prevention, and, therefore, proteostasis maintenance.
authors.affiliation: Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, UMR 3525, F-75724 Paris Cedex 15, France.|Sorbonne Universités, UPMC Paris 6, Complexité Du Vivant, 75252 Paris Cedex 05, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Defenouillère
authors.affiliation: Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, UMR 3525, F-75724 Paris Cedex 15, France.
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Namane
authors.affiliation: Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, UMR 3525, F-75724 Paris Cedex 15, France.
authors.forename: John
authors.initials: J
authors.lastname: Mouaikel
authors.affiliation: Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, UMR 3525, F-75724 Paris Cedex 15, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquier
authors.affiliation: Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, UMR 3525, F-75724 Paris Cedex 15, France mfromont@pasteur.fr.
authors.forename: Micheline
authors.initials: M
authors.lastname: Fromont-Racine
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D010443:Peptide Chain Termination, Translational / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology; D014176:Protein Biosynthesis; D059748:Proteolysis; D016601:RNA-Binding Proteins / Q000378:metabolism; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism* / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D010455:Peptides; D016601:RNA-Binding Proteins; C577644:Rqc1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C115246:TOM1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex