Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain.
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain
Open Biol. 2018 Nov 28;8(11):180155. doi: 10.1098/rsob.180155.
Beyond the general cap-dependent translation initiation, eukaryotic organisms use alternative mechanisms to initiate protein synthesis. Internal ribosome entry site (IRES) elements are -acting RNA regions that promote internal initiation of translation using a cap-independent mechanism. However, their lack of primary sequence and secondary RNA structure conservation, as well as the diversity of host factor requirement to recruit the ribosomal subunits, suggest distinct types of IRES elements. In spite of this heterogeneity, conserved motifs preserve sequences impacting on RNA structure and RNA-protein interactions important for IRES-driven translation. This conservation brings the question of whether IRES elements could consist of basic building blocks, which upon evolutionary selection result in functional elements with different properties. Although RNA-binding proteins (RBPs) perform a crucial role in the assembly of ribonucleoprotein complexes, the versatility and plasticity of RNA molecules, together with their high flexibility and dynamism, determines formation of macromolecular complexes in response to different signals. These properties rely on the presence of short RNA motifs, which operate as modular entities, and suggest that decomposition of IRES elements in short modules could help to understand the different mechanisms driven by these regulatory elements. Here we will review evidence suggesting that model IRES elements consist of the combination of short modules, providing sites of interaction for ribosome subunits, eIFs and RBPs, with implications for definition of criteria to identify novel IRES-like elements genome wide.
除了普遍的帽依赖性翻译起始外，真核生物还使用其他机制来起始蛋白质合成。内部核糖体进入位点（IRES）元件是作用于 RNA 的区域，通过非依赖性帽结构的机制促进翻译的内部起始。然而，它们缺乏主要序列和二级 RNA 结构的保守性，以及招募核糖体亚基所需的宿主因子的多样性，表明存在不同类型的 IRES 元件。尽管存在这种异质性，但保守基序保留了影响 RNA 结构和 RNA-蛋白质相互作用的序列，这些序列对 IRES 驱动的翻译至关重要。这种保守性带来了一个问题，即 IRES 元件是否可以由基本构建块组成，这些构建块经过进化选择，产生具有不同特性的功能元件。尽管 RNA 结合蛋白（RBPs）在核糖核蛋白复合物的组装中发挥着至关重要的作用，但 RNA 分子的多功能性和可塑性，以及它们的高灵活性和动态性，决定了它们能够根据不同的信号形成大分子复合物。这些特性依赖于短 RNA 基序的存在，这些基序作为模块化实体发挥作用，并表明将 IRES 元件分解为短模块可能有助于理解这些调节元件驱动的不同机制。在这里，我们将回顾表明模型 IRES 元件由短模块的组合组成的证据，这些短模块为核糖体亚基、eIF 和 RBPs 提供了相互作用位点，这对定义识别全基因组中新型 IRES 样元件的标准具有重要意义。
