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Deconstructing internal ribosome entry site elements: an update of structural motifs and functional divergences

机译:解构内部核糖体入口部位元素:结构主题的更新和功能分歧

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Beyond the general cap-dependent translation initiation, eukaryotic organisms use alternative mechanisms to initiate protein synthesis. Internal ribosome entry site (IRES) elements are cis-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.
机译:除了一般帽依赖性翻译引发之外,真核生物使用替代机制来引发蛋白质合成。内部核糖体进入部位(IRES)元素是CIS作用RNA区域,其使用帽无关机制促进翻译的内部启动。然而,它们缺乏初级序列和二级RNA结构保护以及患有核糖体亚基的宿主因子要求的多样性,表明了不同类型的IRES元素。尽管存在这种异质性,但保守的基序保持影响对RNA结构和RNA-蛋白质相互作用对IRES驱动的翻译的重要性。这种保护带来了IRES元件是否可以由基本构建块组成的问题,这在进化选择下导致具有不同性质的功能元素。虽然RNA结合蛋白(RBPS)在核糖核糖蛋白复合物组合中表现了至关重要的作用,但RNA分子的多功能性和可塑性以及其高柔韧性和动力,确定了响应于不同信号的大分子复合物的形成。这些属性依赖于短RNA主题的存在,该图案作为模块化实体操作,并表明在短模块中的IRES元件的分解可以有助于了解这些调节元件驱动的不同机制。在这里,我们将审查显示模型IRES元件的证据包括短模块的组合,为核糖体亚基,EIF和RBPS提供相互作用的部位,具有对标准的定义来识别新型IRES样元素基因组的影响。

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