Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-Based translation factor
Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-Based translation factor
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DOI：
10.1016/j.cell.2004.08.001
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发表时间：
2004-08-20
期刊：
影响因子：
64.5
通讯作者：
Frank, J
中科院分区：
文献类型：
--
作者：
Spahn, CMT;Jan, E;Frank, J
真核生物中蛋白质合成的内部启动是通过将核糖体募集到结构化内部核糖体进入位点 (IRES) 来完成的，该位点位于某些病毒和细胞信使 RNA 中。蟋蟀麻痹病毒 (CrPV) 中的 IRES 元件可以在缺乏经典起始因子和起始 tRNA 的情况下直接组装 80S 核糖体。在这里，我们展示了与人核糖体 40S 亚基和 80S 核糖体结合的 CrPV IRES 的冷冻电镜结构。 CrPV IRES 在核糖体亚基间空间内采用明确的细长结构，并与核糖体 A、P 和 E 位点的成分形成特定接触。核糖体以及 IRES 本身的构象变化表明 CrPV IRES 主动操纵核糖体。 CrPV 类 IRES 元件似乎充当基于 RNA 的翻译因子。
Internal initiation of protein synthesis in eukaryotes is accomplished by recruitment of ribosomes to structured internal ribosome entry sites (IRESs), which are located in certain viral and cellular messenger RNAs. An IRES element in cricket paralysis virus (CrPV) can directly assemble 80S ribosomes in the absence of canonical initiation factors and initiator tRNA. Here we present cryo-EM structures of the CrPV IRES bound to the human ribosomal 40S subunit and to the 80S ribosome. The CrPV IRES adopts a defined, elongate structure within the ribosomal intersubunit space and forms specific contacts with components of the ribosomal A, P, and E sites. Conformational changes in the ribosome as well as within the IRES itself show that CrPV IRES actively manipulates the ribosome. CrPV-Iike IRES elements seem to act as RNA-based translation factors.