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Abstract: The ribosome recognizes non-AUG start codons to initiate synthesis of proteins, of antigenic peptides presented by MHC class I molecules (pMHC I), and comprise the dominant initiation events in mammalian 5’-untranslated regions. Yet, even at non-AUG start codons the long-standing model of translation indicates that only one initiator tRNA, Met-tRNAiMet, functions at the initiation step of translation. We describe, however, an unconventional translation initiation event that allows CUG start codons to utilize a leucine-bound tRNA to initiate translation of antigenic precursors. CUG/leucine initiation represents a distinct translation mechanism that can function independently of the classical AUG/eIF2•Met-tRNAiMet pathway, yet requires expression of the non-canonical eukaryotic initiation factor 2A (eIF2A). Thus, a tRNA-based translation initiation mechanism directs non-AUG-initiated protein synthesis and supplies peptides for presentation by MHC class I molecules. These results support the notion that unanticipated and diverse translational mechanisms exist to shape the proteome.

Department:  Biology

Contact: May Chin | 650-725-1827 | maychin@staford.edu

Presenter(s):

• Shelley R. Starck UC Berkeley

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