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Global proteogenomic analysis of human MHC I peptides derived from non­canonical reading frames

ABSTRACT: Using high­throughput mass spectrometry, we probed the six­reading­frame translation of human B cells’ transcriptome. We report that about 10% of MHC I­associated peptides (MAPs) derive from non­canonical reading frames. These so­called cryptic MAPs originate from allegedly non- coding genomic sequences and from out­of­frame translation. Their biogenesis and properties differ in many ways from those of conventional MAPs. Thus, cryptic MAPs come from very short proteins with atypical C­termini, and they are coded by transcripts bearing long UTRs selectively enriched in destabilizing elements. Cryptic MAPs increase the complexity of the immunopeptidome and represent an heretofore unexploited source of potential tumor­specific epitopes. In a more general context, the features of cryptic MAPs suggest that mRNA instability is instrumental in the biogenesis of MAPs. Associated RNA-seq accession: GSE67174 .

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo sapiens  

TISSUE(S): Cell Culture

DISEASE(S): Not Available

SUBMITTER: Olivier Caron-Lizotte  

LAB HEAD: Olivier Caron-Lizotte

PROVIDER: PXD001898 | Pride | 2016-01-28


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Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames.

Laumont Céline M CM   Daouda Tariq T   Laverdure Jean-Philippe JP   Bonneil Éric É   Caron-Lizotte Olivier O   Hardy Marie-Pierre MP   Granados Diana P DP   Durette Chantal C   Lemieux Sébastien S   Thibault Pierre P   Perreault Claude C  

Nature communications 20160105

In view of recent reports documenting pervasive translation outside of canonical protein-coding sequences, we wished to determine the proportion of major histocompatibility complex (MHC) class I-associated peptides (MAPs) derived from non-canonical reading frames. Here we perform proteogenomic analyses of MAPs eluted from human B cells using high-throughput mass spectrometry to probe the six-frame translation of the B-cell transcriptome. We report that ∼ 10% of MAPs originate from allegedly nonc  ...[more]

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