Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I
Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I
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DOI：
10.1126/science.1220270
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发表时间：
2012-06-29
期刊：
影响因子：
56.9
通讯作者：
Shastri, Nilabh
中科院分区：
文献类型：
--
作者：
Starck, Shelley R.;Jiang, Vivian;Shastri, Nilabh
细胞毒性T细胞进行有效的免疫监视需要新合成的多肽由主要组织相容性复合体（MHC）I类分子呈递。这些多肽不仅由常规的以AUG起始的阅读框产生，也由隐蔽的非AUG起始的阅读框通过不同的翻译机制产生。对CUG与AUG起始密码子处的核糖体起始复合物的生化分析表明，细胞使用一种结合亮氨酸的延伸因子转运RNA（Leu - tRNA）在隐蔽的CUG起始密码子处起始翻译。CUG/Leu - tRNA起始不依赖于经典的起始tRNA（AUG/Met - tRNA(i)(Met)）途径，但需要真核起始因子2A的表达。因此，一种基于tRNA的翻译起始机制允许非AUG起始的蛋白质合成，并为MHC I类分子提供呈递的多肽。
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.