2012/06/28 by Shelley R. Starck, Changying Jiang, Mariana Pavon-Eternod +4 · 3 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #RNA and protein synthesis mechanisms #RNA Interference and Gene Delivery #interferon and immune responses
paper · doi:10.1126/science.1220270
openalex publication_date 2012/06/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
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.