Lin Jing-Yi, Brewer Gary, Li Mei-Ling
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Department of Biochemistry & Molecular Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, United States of America.
PLoS One. 2015 Oct 9;10(10):e0140291. doi: 10.1371/journal.pone.0140291. eCollection 2015.
EV71 (enterovirus 71) RNA contains an internal ribosomal entry site (IRES) that directs cap-independent initiation of translation. IRES-dependent translation requires the host's translation initiation factors and IRES-associated trans-acting factors (ITAFs). We reported recently that mRNA decay factor AUF1 is a negative-acting ITAF that binds IRES stem-loop II. We also reported that the small RNA-processing enzyme Dicer produces at least four small RNAs (vsRNAs) from the EV71 IRES. One of these, vsRNA1, derived from IRES stem-loop II, reduces IRES activity and virus replication. Since its mechanism of action is unknown, we hypothesized that it might control association of ITAFs with the IRES. Here, we identified the mRNA stability factor HuR and the RISC subunit Argonaute 2 (Ago2) as two ITAFs that bind stem-loop II. In contrast to AUF1, HuR and Ago2 promote EV71 IRES activity and virus replication. In vitro RNA-binding assays revealed that vsRNA1 can alter association of Ago2, HuR, and AUF1 with stem-loop II. This presents a possible mechanism by which vsRNA1 could control viral translation and replication.
肠道病毒71型（EV71）RNA含有一个内部核糖体进入位点（IRES），该位点可指导不依赖帽子结构的翻译起始。依赖IRES的翻译需要宿主的翻译起始因子和IRES相关反式作用因子（ITAFs）。我们最近报道，mRNA衰变因子AUF1是一种负性作用的ITAF，它能结合IRES茎环II。我们还报道，小RNA加工酶Dicer可从EV71 IRES产生至少四种小RNA（vsRNAs）。其中一种源自IRES茎环II的vsRNA1可降低IRES活性和病毒复制。由于其作用机制尚不清楚，我们推测它可能控制ITAFs与IRES的结合。在此，我们鉴定出mRNA稳定性因子HuR和RNA诱导沉默复合体（RISC）亚基AGO2为两种能结合茎环II的ITAFs。与AUF1相反，HuR和AGO2可促进EV71 IRES活性和病毒复制。体外RNA结合试验表明，vsRNA1可改变AGO2、HuR和AUF1与茎环II的结合。这提出了一种vsRNA1可能控制病毒翻译和复制的潜在机制。
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