Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
EMBO J. 2011 Aug 26;30(21):4423-36. doi: 10.1038/emboj.2011.306.
Picornavirus mRNAs contain IRESs that sustain their translation during infection, when host protein synthesis is shut off. The major classes of picornavirus IRESs (Types 1 and 2) have distinct structures and sequences, but initiation on both is determined by their specific interaction with eIF4G. We report here that Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae, contains an IRES that differs structurally from Type 1 and Type 2 IRESs. Its function similarly involves interaction with eIF4G, but its eIF4G-interacting domain is structurally distinct, although it contains an apical eIF4G-interacting motif similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function is enhanced by pyrimidine tract-binding protein (PTB), but the pattern of PTB's interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of its initiation codon in a stable hairpin.
小核糖核酸病毒的 mRNA 含有 IRES,可在感染期间维持翻译,此时宿主蛋白合成被关闭。小核糖核酸病毒 IRES 的主要类别(类型 1 和 2)具有不同的结构和序列,但两者的起始都由其与 eIF4G 的特异性相互作用决定。我们在这里报告称,Aichivirus(AV),小核糖核酸病毒科 Kobuvirus 属的成员,含有与 1 型和 2 型 IRES 结构不同的 IRES。它的功能同样涉及与 eIF4G 的相互作用,但它的 eIF4G 相互作用域在结构上是不同的,尽管它含有一个与 2 型 IRES 相似的顶端 eIF4G 相互作用基序。与 1 型和 2 型 IRES 一样,AV IRES 功能增强依赖于嘧啶序列结合蛋白(PTB),但 PTB 与每个 IRES 的相互作用模式是不同的。与所有已知的 IRES 不同,AV IRES 绝对依赖于 DHX29,这是由于其起始密码子被稳定发夹封闭而产生的需求。