title: Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I.
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.
authors: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors: Shelley R
authors: SR
authors: Starck
authors: Vivian
authors: V
authors: Jiang
authors: Mariana
authors: M
authors: Pavon-Eternod
authors: Sharanya
authors: S
authors: Prasad
authors: Brian
authors: B
authors: McCarthy
authors: Tao
authors: T
authors: Pan
authors: Nilabh
authors: N
authors: Shastri
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D000938:Antigen-Presenting Cells / Q000276:immunology; D019556:COS Cells; D002522:Chlorocebus aethiops; D018387:Codon, Initiator; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010442:Peptide Chain Initiation, Translational; D014176:Protein Biosynthesis / Q000235:genetics*; D012356:RNA, Transfer, Leu; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018387:Codon, Initiator; D015395:Histocompatibility Antigens Class I; D012356:RNA, Transfer, Leu