Brennan C M, Steitz J A
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Cell Mol Life Sci. 2001 Feb;58(2):266-77. doi: 10.1007/PL00000854.
An important mechanism of posttranscriptional gene regulation in mammalian cells is the rapid degradation of messenger RNAs (mRNAs) signaled by AU-rich elements (AREs) in their 3' untranslated regions. HuR, a ubiquitously expressed member of the Hu family of RNA-binding proteins related to Drosophila ELAV, selectively binds AREs and stabilizes ARE-containing mRNAs when overexpressed in cultured cells. This review discusses mRNA decay as a general form of gene regulation, decay signaled by AREs, and the role of HuR and its Hu-family relatives in antagonizing this mRNA degradation pathway. The influence of newly identified protein ligands to HuR on HuR function in both normal and stressed cells may explain how ARE-mediated mRNA decay is regulated in response to environmental change.
哺乳动物细胞中转录后基因调控的一个重要机制是信使核糖核酸(mRNA)在其3'非翻译区富含AU元件(ARE)所引发的快速降解。HuR是与果蝇胚胎致死异常视觉蛋白(ELAV)相关的Hu家族RNA结合蛋白中普遍表达的成员,在培养细胞中过表达时,它能选择性地结合ARE并稳定含ARE的mRNA。本综述讨论了作为基因调控一般形式的mRNA降解、由ARE引发的降解,以及HuR及其Hu家族相关蛋白在对抗这种mRNA降解途径中的作用。新发现的HuR蛋白配体对正常和应激细胞中HuR功能的影响,可能解释了ARE介导的mRNA降解如何响应环境变化而受到调控。