Most eukaryotic mRNAs are translated in a cap-dependent fashion; however, under stress conditions, the cap-independent translation driven by internal ribosomal entry sites (IRESs) can serve as an alternative mechanism for protein production. Many IRESs have been discovered from viral or cellular mRNAs to promote ribosome assembly and initiate translation by recruiting different trans-acting factors. Although the mechanisms of translation initiation driven by viral IRESs are relatively well understood, the existence of cellular IRESs is still under debate due to the limitations of translation reporter systems used to assay IRES activities. A recent screen identified > 1000 putative IRESs from viral and human mRNAs, expanding the scope and mechanism for cap-independent translation. Additionally, a large number of circular RNAs lacking free ends were identified in eukaryotic cells, many of which are found to be translated through IRESs. These findings suggest that IRESs may play a previously unappreciated role in driving translation of the new type of mRNA, implying a hidden proteome produced from cap-independent translation.

中文翻译：

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IRES 介导的帽独立翻译，一条通往隐藏蛋白质组的路径。


大多数真核生物 mRNA 都是以帽子依赖性方式翻译的。然而，在应激条件下，由内部核糖体进入位点（IRES）驱动的帽独立翻译可以作为蛋白质生产的替代机制。已从病毒或细胞mRNA中发现许多IRES通过招募不同的反式作用因子来促进核糖体组装并启动翻译。尽管病毒 IRES 驱动的翻译起始机制相对较好地了解，但由于用于测定 IRES 活性的翻译报告系统的局限性，细胞 IRES 的存在仍然存在争议。最近的一项筛选从病毒和人类 mRNA 中鉴定出 > 1000 个假定的 IRES，扩大了帽独立翻译的范围和机制。此外，在真核细胞中鉴定出大量缺乏游离末端的环状RNA，其中许多被发现是通过IRES进行翻译的。这些发现表明，IRES 在驱动新型 mRNA 的翻译过程中可能发挥着以前未被认识到的作用，这意味着不依赖帽的翻译产生了隐藏的蛋白质组。