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The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting

Quentin Defenouillère1,2, Abdelkader Namane1, John Mouaikel1

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

Molecular Biology of the Cell
|March 17, 2017
PubMed

Insights

The ribosome-bound quality control (RQC) complex targets defective proteins. A new study reveals Tom1

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Protein Homeostasis

Background:

  • Protein quality control is crucial for preventing cellular damage from misfolded or aggregated proteins.
  • The ribosome-bound quality control (RQC) complex identifies and processes aberrant nascent polypeptides stalled during translation.
  • The RQC complex mediates polyubiquitylation and Cdc48-dependent extraction of stalled peptides for proteasomal degradation.

Purpose of the Study:

  • To elucidate the mechanism of proteasomal degradation for RQC-targeted aberrant peptides.
  • To identify novel components and functions within the protein quality control pathway.
  • To understand the role of Tom1 in handling defective translation products.

Main Methods:

  • Biochemical assays to characterize RQC complex assembly and function.
  • Identification of protein-protein interactions involving the RQC complex and Tom1.
  • Analysis of protein aggregation and accumulation in yeast strains with altered RQC and Tom1 components.

Main Results:

  • The RQC complex exists in both ribosome-bound and ribosome-unbound forms during peptide processing.
  • The E3 ubiquitin ligase Tom1 interacts with aberrant nascent peptides and is recruited by the unbound RQC complex.
  • Tom1 is essential for preventing the accumulation and aggregation of defective peptides, independent of its ligase activity.

Conclusions:

  • Tom1 plays a novel role in protein quality control by interacting with aberrant peptides.
  • Tom1 contributes to aggregate prevention, thereby supporting proteostasis maintenance.
  • These findings reveal new mechanisms for managing translation errors and preventing proteotoxicity.

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