The mechanism of ribosomal recruitment during translation initiation on Type 2 IRESs.

bioRxiv : the preprint server for biology Pub Date : 2025-06-11 DOI:10.1101/2025.06.11.659010

Sayan Bhattacharjee, Irina S Abaeva, Zuben P Brown, Yani Arhab, Hengameh Fallah, Christopher U T Hellen, Joachim Frank, Tatyana V Pestova

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Abstract

The encephalomyocarditis virus (EMCV) IRES and other Type 2 IRESs comprise domains H-L and specifically interact with eIF4G/eIF4A through their essential JK domain. However, the JK domain is not sufficient for IRES function, which also requires the preceding domain I of unknown function. To identify interactions that drive ribosomal recruitment of eIF4G/eIF4A-bound Type 2 IRESs, we determined the cryo-EM structure of 48S initiation complexes formed on the EMCV IRES. It revealed that the apical domain I cloverleaf contacts ribosomal proteins uS13 and uS19 via its Id subdomain and that the essential GNRA tetraloop in subdomain Ic interacts directly with the TψC domain of initiator tRNA. Functional assays supported the exceptional role of these interactions for initiation on this IRES. The strong conservation of primary and secondary structures of the apex of domain I among Type 2 IRESs suggests that the reported interactions are a common essential feature of them all.

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2型IRESs翻译起始时核糖体募集的机制。

脑心肌炎病毒（EMCV） IRES和其他2型IRES包含H-L结构域，并通过其必需的JK结构域特异性地与eIF4G/eIF4A相互作用。但是，对于IRES函数，JK域是不够的，它还需要前面未知函数的域I。为了确定驱动eIF4G/ eif4a结合的2型IRES核糖体募集的相互作用，我们确定了EMCV IRES上形成的48S起始复合物的低温电镜结构。结果表明，顶端结构域I三叶草通过其Id子结构域与核糖体蛋白uS13和uS19接触，而子结构域Ic上必需的GNRA四环直接与启动子tRNA的TψC结构域相互作用。功能分析支持这些相互作用在IRES启动中的特殊作用。2型IRESs中I结构域顶端一级和二级结构的强保守性表明，所报道的相互作用是它们共同的基本特征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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bioRxiv : the preprint server for biology

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