Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 8, Pages 4099-4108Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1914401117
Keywords
ribosome-associated quality control; Listerin; MHC-I; immunopeptidome
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Funding
- European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant [749932]
- European Commission 7th Research Framework Program [GA ERC-2012-SyG_318987-ToPAG]
- Marie Curie Actions (MSCA) [749932] Funding Source: Marie Curie Actions (MSCA)
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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.
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