Novartis Institutes for Biomedical Research, Novartis campus, 4002, Basel, Switzerland,
Adv Exp Med Biol. 2011;700:106-23. doi: 10.1007/978-1-4419-7823-3_10.
Gene expression in eukaryotes is subject to extensive regulation at posttranscriptional levels. One of the most important sites of control involves mRNA 3' untranslated regions (3'utrs), which are recognized by RNA-binding proteins (RBPs) and microRNAs (miRNAs). These factors greatly influence translational efficiency and stability of target mRNAs and often also determine their cellular localization. HuR, a ubiquitously expressed member of the ElaV family of RBPs, has been implicated in regulation of stability and translation of over one hundred mRNAs in mammalian cells. Recent data indicate that some of the effects of HuR can be explained by its interplay with miRNAs. Binding of HuR may suppress the inhibitory effect of mirNAs interacting with the 3'UTR and redirect the repressed mRNA to polysomes for active translation. However, HuR can also synergize with miRNAs. The finding that HuR is able to disengage miRNAs from the repressed mrNa, or render them inactive, provides evidence that miRNa regulation is much more dynamic then originally anticipated. In this chapter we review properties of HuR and describe examples of the cross-talk between the protein and miRNAs, with emphasis on response of the regulation to cellular stress.
真核生物的基因表达受到转录后水平的广泛调控。控制的最重要的位点之一涉及 mRNA 3'非翻译区 (3'utr)，它被 RNA 结合蛋白 (RBPs) 和 microRNAs (miRNAs) 识别。这些因素极大地影响了靶 mRNA 的翻译效率和稳定性，并且通常还决定了它们的细胞定位。HuR 是 ElaV 家族中普遍表达的 RBP 成员之一，已被牵连到哺乳动物细胞中超过一百个 mRNA 的稳定性和翻译调节中。最近的数据表明，HuR 的一些作用可以通过它与 miRNAs 的相互作用来解释。HuR 的结合可以抑制与 3'UTR 相互作用的 miRNAs 的抑制作用，并将受抑制的 mRNA 重新定向到多核糖体进行活跃翻译。然而，HuR 也可以与 miRNAs 协同作用。HuR 能够使 miRNAs 从受抑制的 mrna 上脱离，或者使其失活，这一发现为 miRNA 调节比最初预期的更为动态提供了证据。在本章中，我们将回顾 HuR 的特性，并描述蛋白质和 miRNAs 之间的交叉对话的例子，重点是对调节对细胞应激的反应。
