Lemay Jean-François, Lafontaine Daniel A
Département de Biologie, Faculté des sciences, Université de Sherbrooke, 2500, boulevard de l'Université, Sherbrooke (Québec), J1K 2R1 Canada.
Med Sci (Paris). 2006 Dec;22(12):1053-9. doi: 10.1051/medsci/200622121053.
It has long been known that gene regulation is mostly achieved via protein-nucleic acid interactions. However, the role of RNA factors in gene control has been recently growing given the implication of new RNA-based gene regulation mechanisms such as microRNAs and related short-interfering RNAs gene expression inactivation mechanisms. Recent studies have demonstrated that the involvement of RNA in fundamental gene-control processes is even more extensive. Prokaryotic messenger RNAs carry highly structured domains known as riboswitches within their 5'-untranslated regions. Each riboswitch is able to bind with high specificity their cellular target metabolite, without the involvement of a protein cofactor. Upon metabolite binding, the messenger RNA undergoes structural change that will ultimately lead to the modulation of its genetic expression. Riboswitches can alter gene expression at the level of transcription attenuation or translation initiation, and can up- or down-regulate gene expression by harnessing appropriate changes in the mRNA structure. Here, we provide an overview of the adenine riboswitch, one of the smallest riboswitch and one of the few that activates gene expression upon ligand binding. Several crystal structures have been obtained for the ligand-binding domain of this riboswitch providing us with an unprecedented glimpse about how riboswitches use their ligand to regulate gene expression. Moreover, mechanistic studies have recently shed light on the transcriptional regulation mechanisms of the adenine riboswitch suggesting that riboswitches may rely on the kinetics of ligand binding and the speed of RNA transcription, rather than simple ligand affinity. Riboswitches are particularly interesting because RNA-ligand interactions are potentially very important in the elaboration of antimicrobial agents.
长期以来,人们都知道基因调控主要是通过蛋白质 - 核酸相互作用来实现的。然而,鉴于新的基于RNA的基因调控机制(如微小RNA和相关的短干扰RNA基因表达失活机制)的影响,RNA因子在基因控制中的作用近来越来越受到关注。最近的研究表明,RNA在基本基因控制过程中的参与甚至更为广泛。原核生物信使RNA在其5'非翻译区内携带称为核糖开关的高度结构化结构域。每个核糖开关能够高度特异性地结合其细胞靶代谢物,而无需蛋白质辅因子的参与。代谢物结合后,信使RNA会发生结构变化,最终导致其基因表达的调节。核糖开关可以在转录衰减或翻译起始水平改变基因表达,并通过利用mRNA结构的适当变化上调或下调基因表达。在这里,我们概述了腺嘌呤核糖开关,它是最小的核糖开关之一,也是少数几个在配体结合时激活基因表达的核糖开关之一。已经获得了该核糖开关配体结合结构域的几个晶体结构,这使我们前所未有地了解核糖开关如何利用其配体来调节基因表达。此外,机理研究最近揭示了腺嘌呤核糖开关的转录调控机制,表明核糖开关可能依赖于配体结合的动力学和RNA转录的速度,而不是简单的配体亲和力。核糖开关特别有趣,因为RNA - 配体相互作用在抗菌剂的研制中可能非常重要。