Laboratoire de Cristallographie et RMN Biologiques, UMR8015 CNRS / Université Paris Descartes, 4 avenue de l'Observatoire 75270 Paris Cedex, France.
Biochem Soc Trans. 2010 Dec;38(6):1548-52. doi: 10.1042/BST0381548.
Lentiviruses, the prototype of which is HIV-1, can initiate translation either by the classical cap-dependent mechanism or by internal recruitment of the ribosome through RNA domains called IRESs (internal ribosome entry sites). Depending on the virus considered, the mechanism of IRES-dependent translation differs widely. It can occur by direct binding of the 40S subunit to the mRNA, necessitating a subset or most of the canonical initiation factors and/or ITAF (IRES trans-acting factors). Nonetheless, a common feature of IRESs is that ribosomal recruitment relies, at least in part, on IRES structural determinants. Lentiviral genomic RNAs present an additional level of complexity, as, in addition to the 5'-UTR (untranslated region) IRES, the presence of a new type of IRES, embedded within Gag coding region was described recently. This IRES, conserved in all three lentiviruses examined, presents conserved structural motifs that are crucial for its activity, thus reinforcing the link between RNA structure and function. However, there are still important gaps in our understanding of the molecular mechanism underlying IRES-dependent translation initiation of HIV, including the determination of the initiation factors required, the dynamics of initiation complex assembly and the dynamics of the RNA structure during initiation complex formation. Finally, the ability of HIV genomic RNA to initiate translation through different pathways questions the possible mechanisms of regulation and their correlation to the viral paradigm, i.e. translation versus encapsidation of its genomic RNA.
慢病毒，其原型是 HIV-1，可以通过经典的帽依赖性机制或通过 RNA 结构域（称为 IRESs（内部核糖体进入位点））内部招募核糖体来启动翻译。根据所考虑的病毒，IRES 依赖性翻译的机制差异很大。它可以通过 40S 亚基与 mRNA 的直接结合发生，需要一组或大多数规范起始因子和/或 ITAF（IRES 反式作用因子）。尽管如此，IRES 的一个共同特征是核糖体募集至少部分依赖于 IRES 结构决定因素。慢病毒基因组 RNA 呈现出额外的复杂性，除了 5'-UTR（非翻译区）IRES 之外，最近还描述了一种新型 IRES，嵌入 Gag 编码区。该 IRES 在所有三种检查的慢病毒中都保守，具有保守的结构基序，对其活性至关重要，从而加强了 RNA 结构与功能之间的联系。然而，我们对 HIV 中 IRES 依赖性翻译起始的分子机制仍存在重要的理解空白，包括确定所需的起始因子、起始复合物组装的动力学以及起始复合物形成过程中 RNA 结构的动力学。最后，HIV 基因组 RNA 通过不同途径启动翻译的能力质疑了可能的调节机制及其与病毒范例（即翻译与基因组 RNA 的包装）的相关性。
