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

Shelley R. Starck, Vivian Jiang, Mariana Pavon-Eternod, Sharanya Prasad, Brian McCarthy, Tao Pan, Nilabh Shastri

Research output: Contribution to journalArticlepeer-review

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-tRNAiMet) 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.

Original languageEnglish (US)
Pages (from-to)1719-1723
Number of pages5
JournalScience
Volume336
Issue number6089
DOIs
StatePublished - Jun 29 2012
Externally publishedYes

ASJC Scopus subject areas

  • General

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