Laboratory of Molecular Biology and Immunology, NIA-IRP, NIH, Baltimore, MD 21224, USA.
Front Biosci (Landmark Ed). 2012 Jan 1;17(1):189-205. doi: 10.2741/3921.
The cytoplasmic events that control mammalian gene expression, primarily mRNA stability and translation, potently influence the cellular response to internal and external signals. The ubiquitous RNA-binding protein (RBP) HuR is one of the best-studied regulators of cytoplasmic mRNA fate. Through its post-transcriptional influence on specific target mRNAs, HuR can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli. In light of its central role in important cellular functions, HuR's role in diseases in which these responses are aberrant is increasingly appreciated. Here, we review the mechanisms that control HuR function, its influence on target mRNAs, and how impairment in HuR-governed gene expression programs impact upon different disease processes. We focus on HuR's well-recognized implication in cancer and chronic inflammation, and discuss emerging studies linking HuR to cardiovascular, neurological, and muscular pathologies. We also discuss the progress, potential, and challenges of targeting HuR therapeutically.
细胞质事件控制哺乳动物基因表达，主要是 mRNA 的稳定性和翻译，强烈影响细胞对内部和外部信号的反应。普遍存在的 RNA 结合蛋白 (RBP) HuR 是研究细胞质 mRNA 命运的最佳调节因子之一。通过对特定靶 mRNA 的转录后影响，HuR 可以改变细胞对增殖、应激、凋亡、分化、衰老、炎症和免疫刺激的反应。鉴于其在重要细胞功能中的核心作用，HuR 在这些反应异常的疾病中的作用越来越受到重视。在这里，我们回顾了控制 HuR 功能的机制、它对靶 mRNA 的影响，以及 HuR 调控的基因表达程序的损伤如何影响不同的疾病过程。我们重点介绍了 HuR 在癌症和慢性炎症中的公认作用，并讨论了将 HuR 与心血管、神经和肌肉病理学联系起来的新兴研究。我们还讨论了靶向 HuR 治疗的进展、潜力和挑战。
