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 journalArticle

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

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Initiator Codon
Transfer RNA
Major Histocompatibility Complex
Leucine
RNA, Transfer, Met
Peptides
Eukaryotic Initiation Factors
Reading Frames
Proteins
T-Lymphocytes

ASJC Scopus subject areas

  • General

Cite this

Starck, S. R., Jiang, V., Pavon-Eternod, M., Prasad, S., McCarthy, B., Pan, T., & Shastri, N. (2012). Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. Science, 336(6089), 1719-1723. https://doi.org/10.1126/science.1220270

Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. / Starck, Shelley R.; Jiang, Vivian; Pavon-Eternod, Mariana; Prasad, Sharanya; McCarthy, Brian; Pan, Tao; Shastri, Nilabh.

In: Science, Vol. 336, No. 6089, 29.06.2012, p. 1719-1723.

Research output: Contribution to journalArticle

Starck, SR, Jiang, V, Pavon-Eternod, M, Prasad, S, McCarthy, B, Pan, T & Shastri, N 2012, 'Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I', Science, vol. 336, no. 6089, pp. 1719-1723. https://doi.org/10.1126/science.1220270
Starck SR, Jiang V, Pavon-Eternod M, Prasad S, McCarthy B, Pan T et al. Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. Science. 2012 Jun 29;336(6089):1719-1723. https://doi.org/10.1126/science.1220270
Starck, Shelley R. ; Jiang, Vivian ; Pavon-Eternod, Mariana ; Prasad, Sharanya ; McCarthy, Brian ; Pan, Tao ; Shastri, Nilabh. / Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. In: Science. 2012 ; Vol. 336, No. 6089. pp. 1719-1723.
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