Proteomics

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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 (human)

TISSUE(S): B Cell, Cell Culture

SUBMITTER: Olivier Caron-Lizotte  

LAB HEAD: Olivier Caron-Lizotte

PROVIDER: PXD001898 | Pride | 2016-01-28

REPOSITORIES: Pride

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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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