Section of Pharmacology, Department of Drug Sciences, University of Pavia, Via Taramelli 14, 27100, Pavia, Italy.
Cell Mol Life Sci. 2012 Feb;69(4):501-17. doi: 10.1007/s00018-011-0810-7. Epub 2011 Sep 10.
Post-transcriptional mechanisms are key determinants in the modulation of the expression of final gene products. Within this context, fundamental players are RNA-binding proteins (RBPs), and among them ELAV-like proteins. RBPs are able to affect every aspect in the processing of transcripts, from alternative splicing, polyadenylation, and nuclear export to cytoplasmic localization, stability, and translation. Of interest, more than one RBP can bind simultaneously the same mRNA; therefore, since each RBP is endowed with different properties, the balance of these interactions dictates the ultimate fate of the transcript, especially in terms of both stability and rate of translation. Besides RBPs, microRNAs are also important contributors to the post-transcriptional control of gene expression. Within this general context, the present review focuses on ELAV-like proteins describing their roles in the nucleus and in the cytoplasm, also highlighting some examples of interactions with other RBPs and with microRNAs. We also examine the putative role and the observed changes of ELAV-like proteins and of their interactions with other regulatory elements in Alzheimer's disease, cancer, and inflammation. The changes in the expression of proteins involved in these diseases are examples of how a derangement in the mRNA stabilization process may be associated with disease development and contribute to pathology. Overall, we hope that the topics handled in the present manuscript provide a hint to look at ELAV-like-mediated mRNA stabilization as a mechanism relevant to disease as well as a novel putative drug target.
转录后机制是调节最终基因产物表达的关键决定因素。在这种情况下,基本的参与者是 RNA 结合蛋白 (RBPs),其中包括 ELAV 样蛋白。RBPs 能够影响转录本处理的各个方面,包括可变剪接、多聚腺苷酸化、核输出到细胞质定位、稳定性和翻译。有趣的是,不止一种 RBP 可以同时结合同一 mRNA;因此,由于每个 RBP 都具有不同的特性,这些相互作用的平衡决定了转录本的最终命运,特别是在稳定性和翻译率方面。除了 RBPs 之外,microRNAs 也是基因表达转录后调控的重要贡献者。在这个一般背景下,本综述重点介绍了 ELAV 样蛋白,描述了它们在核内和细胞质中的作用,还强调了与其他 RBPs 和 microRNAs 的一些相互作用的例子。我们还研究了 ELAV 样蛋白及其与其他调节元件相互作用在阿尔茨海默病、癌症和炎症中的潜在作用和观察到的变化。参与这些疾病的蛋白质表达的变化是这样一种情况的例子,即 mRNA 稳定过程的紊乱可能与疾病的发展有关,并有助于病理学。总体而言,我们希望本手稿中涉及的主题能让人们将 ELAV 样蛋白介导的 mRNA 稳定视为一种与疾病相关的机制,以及一种新的潜在药物靶点。