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The ribosome-bound quality control complex: from aberrant peptide clearance to proteostasis maintenance

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Abstract

Proteostasis in eukaryotes is maintained by compartment-specific quality control pathways, which enable the refolding or the degradation of defective polypeptides to prevent the toxicity that may arise from their aggregation. Among these processes, translational protein quality control is performed by the Ribosome-bound Quality Control complex (RQC), which recognizes nascent peptides translated from aberrant mRNAs, polyubiquitylates these aberrant peptides, extracts them from the stalled 60S subunit and finally escorts them to the proteasome for degradation. In this review, we focus on the mechanism of action of the RQC complex from stalled 60S binding to aberrant peptide delivery to the proteasome and describe the cellular consequences of a deficiency in the RQC pathway, such as aberrant protein aggregation. In addition, this review covers the recent discoveries concerning the role of cytosolic chaperones, as well as Tom1, to prevent the accumulation of aberrant protein aggregates in case of a deficiency in the RQC pathway.

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Abbreviations

RQC:

Ribosome-bound Quality Control

PQC:

Protein quality control

eRF:

Eukaryotic recycling factor

RING:

Really interesting new gene

NEMF:

Nuclear export mediator factor

CAT:

C-terminal alanine threonine

HUWE1:

HECT, UBA and WWE domain-containing protein 1

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Acknowledgements

This work was supported by ANR-14-CE-10-0014-01 from the Agence Nationale de la Recherche, the Institut Pasteur, and the Centre National de la Recherche Scientifique. Q.D. was supported by a postdoctoral fellowship from the Fondation pour la Recherche Médicale (SPF20150934065).

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  1. Quentin Defenouillère

    Present address: Membrane Trafficking, Ubiquitin and Signaling, Institut Jacques Monod, UMR7592 CNRS/Université Paris-Diderot, 15 Rue Hélène Brion, Bât. Buffon, 75205, Paris Cedex 13, France

Authors and Affiliations

  1. Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, UMR 3525, 75724, Paris Cedex 15, France

    Quentin Defenouillère & Micheline Fromont-Racine

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  1. Quentin Defenouillère
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  2. Micheline Fromont-Racine
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Correspondence to Quentin Defenouillère.

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Communicated by M. Kupiec.

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Defenouillère, Q., Fromont-Racine, M. The ribosome-bound quality control complex: from aberrant peptide clearance to proteostasis maintenance. Curr Genet 63, 997–1005 (2017). https://doi.org/10.1007/s00294-017-0708-5

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