Internal ribosome entry sites (IRESs) are cis-acting RNA elements capable of recruiting ribosomes and initiating translation on an internal portion of an mRNA. This is divergent from canonical eukaryotic translation initiation, where the 5’ cap is recognized by initiation factors (IFs) that recruit the ribosome to initiate translation of the encoded peptide. All known IRESs are capable of initiating translation in a cap-independent manner, and are therefore not constrained by the absence or presence of a 5’ m⁷G cap. In addition to being cap-independent, IRES-mediated translation often uses only a subset of IFs allowing them to function independently of canonical initiation. The ability to function independently of the canonical translation initiation pathway allows IRESs to mediate gene expression when cap-dependent translation has been inhibited. Recent reports of viral IRESs capable of initiating translation across taxonomic domains (Eukarya and Bacteria) have sparked interest in designing gene expression systems compatible with multiple organisms. The ability to drive translation independent of cellular context using a common mechanism would have a wide range of applications ranging from agriculture biotechnology to the development of antiviral drugs. Here we discuss IRES-mediated translation and critically compare the available mechanistic and structural information. A particular focus will be on IRES-meditated translation across domains of life (viral and cellular IRESs) , IRES bioengineering and the possibility of an evolutionary conserved translation initiation mechanism.

内部核糖体进入位点（IRESs）是顺式作用RNA元件，能够募集核糖体并在mRNA的内部启动翻译。这与经典的真核翻译起始不同，在常规的真核翻译起始中，5'帽被起始因子（IF）识别，该起始因子募集核糖体以起始编码肽的翻译。所有已知的IRESS能够以不依赖帽的方式启动翻译的，并且因此不被的5'米不存在或存在约束⁷G帽 除了独立于上限之外，IRES介导的翻译通常仅使用IF的子集，从而使它们能够独立于规范启动而发挥作用。独立于规范翻译起始途径的功能使IRES在抑制帽依赖性翻译时介导基因表达。能够启动跨生物分类域（真核生物和细菌）翻译的病毒性IRES的最新报道引起了人们对设计与多种生物相容的基因表达系统的兴趣。使用通用机制独立于细胞环境驱动翻译的能力将具有广泛的应用范围，从农业生物技术到抗病毒药物的开发。在这里，我们讨论了IRES介导的翻译，并严格比较了可用的机械和结构信息。将特别关注跨生命域（病毒和细胞IRES），IRES生物工程学以及IRES保守翻译起始机制的可能性的跨IRES的翻译。