RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein
RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein
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DOI：
10.1093/emboj/17.12.3461
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发表时间：
1998-06-15
期刊：
影响因子：
11.4
通讯作者：
Shyu, AB
中科院分区：
文献类型：
--
作者：
Peng, SSY;Chen, CYA;Shyu, AB
转录后调控的一个重要范例是由编码癌蛋白、细胞因子和转录因子的转录物的3'非翻译区中的富含AU的元件（战神）介导的细胞质mRNA稳定性的控制。虽然许多RNA结合蛋白已被证明在体外与战神结合，但它们相互作用的功能后果和生理意义都是未知的。在这里，我们证明了胚胎致死异常视觉（ELAV）RNA结合蛋白HuR在体内mRNA周转的作用。ELAV RNA结合蛋白家族在脊椎动物中高度保守。在人类中，有四个成员; HuR在所有增殖细胞中表达，而Hel-N1，HuC和HuD在终末分化的神经元中表达。我们发现，细胞质HuR水平的升高抑制c-fos ARE介导的RNA衰变，但对c-jun ARE指导的快速衰变几乎没有影响。似乎HuR对去腺苷化的影响不大，但延迟了RNA体衰变的开始并减缓了其随后的衰变。我们还表明，HuR可以被诱导从细胞核重新分布到细胞质，并且这种重新分布与改变的功能有关。通过控制ELAV蛋白在细胞核和细胞质之间的分布来调节ARE介导的衰变途径可能是调节细胞生长和分化的机制。
An important paradigm for post-transcriptional regulation is the control of cytoplasmic mRNA stability mediated by AU-rich elements (AREs) in the 3' untranslated region of transcripts encoding oncoproteins, cytokines and transcription factors. While many RNA-binding proteins have been shown to bind to AREs in vitro, neither the functional consequences nor the physiological significance of their interactions are known. Here we demonstrate a role for the embryonic lethal abnormal visual (ELAV) RNA-binding protein HuR in mRNA turnover in vivo. The ELAV family of RNA-binding proteins is highly conserved in vertebrates. In humans, there are four members; HuR is expressed in all proliferating cells, whereas Hel-N1, HuC and HuD are expressed in terminally differentiated neurons. We show that elevation of cytoplasmic HuR levels inhibits c-fos ARE-mediated RNA decay but has little effect on rapid decay directed by c-jun ARE. It appears that HuR has little effect on deadenylation but delays onset of decay of the RNA body and slows down its subsequent decay, We also show that HuR can be induced to redistribute from the nucleus to the cytoplasm and that this redistribution is associated with an altered function. Modulation of the ARE-mediated decay pathway through controlling distribution of the ELAV proteins between nucleus and cytoplasm may be a mechanism by which cell growth and differentiation is regulated.