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MHC-I peptidome analysis of human foreskin fibroblasts

ABSTRACT: Ribosome profiling (Ribo-seq) recently revealed the expression of thousands of short open reading frames (sORFs) in eukaryotic cells. They encode for a class of instable peptides, which evade experimental validation by whole-proteome mass spectrometry. Here, we show that computational elimination of experimental noise from Ribo-seq data unravels fundamental new aspects of sORF biology. Based on the revised annotation of cellular sORFs, we show that sORF-derived peptides are efficiently incorporated into MHC-I. sORFs thus encode a novel class of stress-responsive antigens in human cells. Our findings have broad implications on the functional, regulatory and immunogenic role of sORFs in fundamental cellular processes like infection and cancer.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell

SUBMITTER: Florian Erhard

LAB HEAD: Stefan Stevanović

PROVIDER: PXD007203 | Pride | 2018-04-05

REPOSITORIES: Pride

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Improved Ribo-seq enables identification of cryptic translation events.

Erhard Florian F Halenius Anne A Zimmermann Cosima C L'Hernault Anne A Kowalewski Daniel J DJ Weekes Michael P MP Stevanovic Stefan S Zimmer Ralf R Dölken Lars L

Nature methods 20180312 5

Ribosome profiling has been used to predict thousands of short open reading frames (sORFs) in eukaryotic cells, but it suffers from substantial levels of noise. PRICE (https://github.com/erhard-lab/price) is a computational method that models experimental noise to enable researchers to accurately resolve overlapping sORFs and noncanonical translation initiation. We experimentally validated translation using major histocompatibility complex class I (MHC I) peptidomics and observed that sORF-deriv ...[more]

PMID: 29529017

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