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Science. 2012 Jun 29;336(6089):1719-23. doi: 10.1126/science.1220270.

Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I.

Author information

1
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

Abstract

Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non-AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons. CUG/Leu-tRNA initiation was independent of the canonical initiator tRNA (AUG/Met-tRNA(i)(Met)) pathway but required expression of eukaryotic initiation factor 2A. Thus, a tRNA-based translation initiation mechanism allows non-AUG-initiated protein synthesis and supplies peptides for presentation by MHC class I molecules.

PMID:
22745432
DOI:
10.1126/science.1220270
[Indexed for MEDLINE]
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