The pathway of HCVIRES-mediated translation initiation
The pathway of HCVIRES-mediated translation initiation
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DOI：
10.1016/j.cell.2004.09.038
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发表时间：
2004-10-29
期刊：
影响因子：
64.5
通讯作者：
Puglisi, JD
中科院分区：
文献类型：
--
作者：
Otto, GA;Puglisi, JD
HCV 内部核糖体进入位点 (IRES) 通过与典型真核起始不同的顺序途径直接调节病毒 mRNA 上翻译起始复合物的组装。 HCV IRES 可以与不含 eIF 的 40S 核糖体亚基形成二元复合物。接下来，eIF3 和三元复合物结合后，48S 样复合物在 AUG 起始密码子处组装。 80S 复合体的形成具有速率限制，并遵循 60S 亚基的 GTP 依赖性关联。 IRES mRNA 上 48S 样和 80S 复合物的有效组装取决于高度保守的 HCV IRES 结构的维持。这种 HCV IRES 翻译起始的修订模型为理解翻译起始期间不同 HCV IRES 结构域的功能提供了背景。
The HCV internal ribosome entry site (IRES) directly regulates the assembly of translation initiation complexes on viral mRNA by a sequential pathway that is distinct from canonical eukaryotic initiation. The HCV IRES can form a binary complex with an eIF-free 40S ribosomal subunit. Next, a 48S-like complex assembles at the AUG initiation codon upon association of eIF3 and ternary complex. 80S complex formation is rate limiting and follows the GTP-dependent association of the 60S subunit. Efficient assembly of the 48S-like and 80S complexes on the IRES mRNA is dependent upon maintenance of the highly conserved HCV IRES structure. This revised model of HCV IRES translation initiation provides a context to understand the function of different HCV IRES domains during translation initiation.