Role for ribosome-associated quality control in sampling proteins for MHC class I-mediated antigen presentation

Debora Broch Trentini, Matteo Pecoraro, Shivani Tiwary, Juergen Cox, Matthias Mann, Mark S. Hipp*, Ulrich Hartl

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)
41 Downloads (Pure)

Abstract

Mammalian cells present a fingerprint of their proteome to the adaptive immune system through the display of endogenous peptides on MHC-I complexes. MHC-I-bound peptides originate from protein degradation by the proteasome, suggesting that stably folded, long-lived proteins could evade monitoring. Here, we investigate the role in antigen presentation of the ribosome-associated quality control (RQC) pathway for the degradation of nascent polypeptides that are encoded by defective messenger RNAs and undergo stalling at the ribosome during translation. We find that degradation of model proteins by RQC results in efficient MHC-I presentation, independent of their intrinsic folding properties. Quantitative profiling of MHC-I peptides in wild-type and RQC-deficient cells by mass spectrometry showed that RQC substantially contributes to the composition of the immunopeptidome. Our results also identify endogenous substrates of the RQC pathway in human cells and provide insight into common principles causing ribosome stalling under physiological conditions.

Original languageEnglish
Pages (from-to)4099-4108
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number8
DOIs
Publication statusPublished - 25-Feb-2020
Externally publishedYes

Keywords

  • ribosome-associated quality control
  • Listerin
  • MHC-I
  • immunopeptidome
  • COMBINED TRANSMEMBRANE TOPOLOGY
  • MESSENGER-RNA SURVEILLANCE
  • SIGNAL PEPTIDE PREDICTION
  • E3 UBIQUITIN LIGASE
  • ZIKA VIRUS
  • ENDONUCLEOLYTIC CLEAVAGE
  • STALLED RIBOSOME
  • MATURE PROTEINS
  • CELL-PROTEINS
  • ER MEMBRANE

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