Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Cell Host Microbe. 2011 Jan 20;9(1):58-69. doi: 10.1016/j.chom.2010.12.001.
Viruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.
病毒依赖宿主翻译机制来完成其生命周期。微小 RNA-141 诱导的翻译起始因子 eIF4E 对宿主蛋白合成的关闭。在这里，我们描述了另一种机制，微小 RNA-141 诱导的翻译起始因子 eIF4E 在微小 RNA-141 反义寡核苷酸对病毒复制的抑制作用。微小 RNA-141 的下调减少了病毒的复制，而 eIF4E 的沉默可以完全逆转微小 RNA-141 反义寡核苷酸对病毒复制的抑制作用。微小 RNA-141 的异位表达促进了从依赖帽子到依赖帽子的翻译的转换。此外，我们鉴定了一个转录因子 EGR1，它部分负责对肠道病毒感染的微小 RNA-141 的诱导。我们的结果表明，肠道病毒感染时微小 RNA-141 的上调可以通过加速翻译转换来促进病毒的增殖。
