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A distinct translation initiation mechanism generates cryptic peptides for immune surveillance.

ABSTRACT: MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance.

SUBMITTER: Starck SR

PROVIDER: S-EPMC2565129 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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A distinct translation initiation mechanism generates cryptic peptides for immune surveillance.

Starck Shelley R SR Ow Yongkai Y Jiang Vivian V Tokuyama Maria M Rivera Mark M Qi Xin X Roberts Richard W RW Shastri Nilabh N

PloS one 20081021 10

MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexe ...[more]

PMID: 18941630

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