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.
journal_name
Proc Natl Acad Sci U S Aauthors
Trentini DB,Pecoraro M,Tiwary S,Cox J,Mann M,Hipp MS,Hartl FUdoi
10.1073/pnas.1914401117subject
Has Abstractpub_date
2020-02-25 00:00:00pages
4099-4108issue
8eissn
0027-8424issn
1091-6490pii
1914401117journal_volume
117pub_type
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