Most non-canonical proteins uniquely populate the proteome or immunopeptidome.
Cell Line, Tumor
Chromatography, High Pressure Liquid
Histocompatibility Antigens Class I
/ genetics
Humans
Lymphoma, B-Cell
/ metabolism
Open Reading Frames
/ genetics
Protein Isoforms
/ metabolism
Proteome
/ analysis
Ribosomes
/ metabolism
Sequence Analysis, RNA
Signal Transduction
/ genetics
Tandem Mass Spectrometry
computational biology
defective ribosomal products
major histocompatibility complex
mass spectrometry
non-canonical translation
peptides
protein isoforms
proteomic methods
ribosome profiling
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
09 03 2021
09 03 2021
Historique:
received:
03
08
2020
revised:
29
01
2021
accepted:
10
02
2021
entrez:
10
3
2021
pubmed:
11
3
2021
medline:
27
1
2022
Statut:
ppublish
Résumé
Combining RNA sequencing, ribosome profiling, and mass spectrometry, we elucidate the contribution of non-canonical translation to the proteome and major histocompatibility complex (MHC) class I immunopeptidome. Remarkably, of 14,498 proteins identified in three human B cell lymphomas, 2,503 are non-canonical proteins. Of these, 28% are novel isoforms and 72% are cryptic proteins encoded by ostensibly non-coding regions (60%) or frameshifted canonical genes (12%). Cryptic proteins are translated as efficiently as canonical proteins, have more predicted disordered residues and lower stability, and critically generate MHC-I peptides 5-fold more efficiently per translation event. Translating 5' "untranslated" regions hinders downstream translation of genes involved in transcription, translation, and antiviral responses. Novel protein isoforms show strong enrichment for signaling pathways deregulated in cancer. Only a small fraction of cryptic proteins detected in the proteome contribute to the MHC-I immunopeptidome, demonstrating the high preferential access of cryptic defective ribosomal products to the class I pathway.
Identifiants
pubmed: 33691108
pii: S2211-1247(21)00129-7
doi: 10.1016/j.celrep.2021.108815
pmc: PMC8040094
mid: NIHMS1683085
pii:
doi:
Substances chimiques
Histocompatibility Antigens Class I
0
Protein Isoforms
0
Proteome
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108815Subventions
Organisme : Intramural NIH HHS
ID : ZIA AI000653
Pays : United States
Organisme : CIHR
ID : FDN 148400
Pays : Canada
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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