Most non-canonical proteins uniquely populate the proteome or immunopeptidome

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.,

Publication
Cell Reports
Mathieu Courcelles
Mathieu Courcelles
Étudiant au doctorat en bio-informatique (2008-2012 avec Pierre Thibault, IRIC)
Sébastien Lemieux
Sébastien Lemieux
Chercheur principal

Chercheur principal, Unité de recherche en bio-informatique fonctionnelle et structurale, IRIC | Direction scientifique de la plateforme de Bio-informatique | Professeur agrégé, Département de biochimie et médecine moléculaire, Université de Montréal