Laboratoire de Biologie moléculaire du gène, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 12 rue des Profs. Jeener et Brachet, Gosselies 6041, Belgium.
Laboratoire de Biologie moléculaire du gène, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 12 rue des Profs. Jeener et Brachet, Gosselies 6041, Belgium.
Biochem Pharmacol. 2014 Jun 15;89(4):431-40. doi: 10.1016/j.bcp.2014.04.003. Epub 2014 Apr 13.
Initially identified as an occasional and peculiar mode of gene regulation in eukaryotes, RNA-binding protein-mediated post-transcriptional control of gene expression has emerged, over the last two decades, as a major contributor in the control of gene expression. A large variety of RNA-binding proteins (RBPs) allows the recognition of very diverse messenger RNA sequences and participates in the regulation of basically all cellular processes. Nevertheless, the rapid outcome of post-transcriptional regulations on the level of gene expression has favored the expansion of this type of regulation in cellular processes prone to rapid and frequent modulations such as the control of the inflammatory response. At the molecular level, the 3'untranslated region (3'UTR) of mRNA is a favored site of RBP recruitment. RBPs binding to these regions control gene expression through two major modes of regulation, namely mRNA decay and modulation of translational activity. Recent progresses suggest that these two mechanisms are often interdependent and might result one from the other. Therefore, different RBPs binding distinct RNA subsets could share similar modes of action at the molecular level. RBPs are frequent targets of post-translational modifications, thereby disclosing numerous possibilities for pharmacological interventions. However, redundancies of the transduction pathways controlling these modifications have limited the perspectives to define RBPs as new therapeutic targets. Through the analysis of several examples of RBPs binding to 3'untranslated region of mRNA, we present here recent progress and perspectives regarding this rapidly evolving field of molecular biology.
最初被认为是真核生物中一种偶然的、特殊的基因调控方式，在过去的二十年中，RNA 结合蛋白介导的基因表达转录后调控已成为基因表达调控的主要贡献者。大量的 RNA 结合蛋白 (RBPs) 允许识别非常多样化的信使 RNA 序列，并参与基本上所有细胞过程的调控。然而，转录后调控在基因表达水平上的快速结果促进了这种类型的调控在细胞过程中的扩展，这些过程容易发生快速和频繁的调节，如炎症反应的控制。在分子水平上，mRNA 的 3'非翻译区 (3'UTR) 是 RBP 募集的首选部位。与这些区域结合的 RBPs 通过两种主要的调控模式来控制基因表达，即 mRNA 降解和翻译活性的调节。最近的进展表明，这两种机制通常是相互依赖的，可能相互作用。因此，不同的 RBP 结合不同的 RNA 子集在分子水平上可能具有相似的作用模式。RBPs 是翻译后修饰的常见靶点，从而为药理学干预提供了许多可能性。然而，控制这些修饰的转导途径的冗余性限制了将 RBPs 定义为新的治疗靶点的可能性。通过对几个 RBPs 结合 mRNA 3'非翻译区的例子进行分析，我们在这里介绍了这个快速发展的分子生物学领域的最新进展和展望。
