Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, CA 95064, USA.
Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1839-44. doi: 10.1073/pnas.1018582108. Epub 2011 Jan 18.
Internal ribosome entry site (IRES) RNAs are elements of viral or cellular mRNAs that bypass steps of canonical eukaryotic cap-dependent translation initiation. Understanding of the structural basis of IRES mechanisms is limited, partially due to a lack of high-resolution structures of IRES RNAs bound to their cellular targets. Prompted by the universal phylogenetic conservation of the ribosomal P site, we solved the crystal structures of proposed P site binding domains from two intergenic region IRES RNAs bound to bacterial 70S ribosomes. The structures show that these IRES domains nearly perfectly mimic a tRNA • mRNA interaction. However, there are clear differences in the global shape and position of this IRES domain in the intersubunit space compared to those of tRNA, supporting a mechanism for IRES action that invokes hybrid state mimicry to drive a noncanonical mode of translocation. These structures suggest how relatively small structured RNAs can manipulate complex biological machines.
内部核糖体进入位点（IRES）RNA 是病毒或细胞 mRNA 的元件，可绕过典型的真核帽依赖性翻译起始步骤。对 IRES 机制的结构基础的理解是有限的，部分原因是缺乏与细胞靶标结合的 IRES RNA 的高分辨率结构。由于核糖体 P 位点的普遍系统发育保守性，我们解决了两个基因间区 IRES RNA 结合到细菌 70S 核糖体的 P 位点结合结构域的晶体结构。这些结构表明，这些 IRES 结构域几乎完美地模拟了 tRNA•mRNA 相互作用。然而，与 tRNA 相比，在亚基间空间中，该 IRES 结构域的全局形状和位置存在明显差异，支持了一种 IRES 作用机制，该机制利用杂种状态模拟来驱动非典型的易位模式。这些结构表明相对较小的结构 RNA 如何能够操纵复杂的生物机器。
