Simone Roberto, Fratta Pietro, Neidle Stephen, Parkinson Gary N, Isaacs Adrian M
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Sobell Department of Motor Neuroscience and Movement, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
FEBS Lett. 2015 Jun 22;589(14):1653-68. doi: 10.1016/j.febslet.2015.05.003. Epub 2015 May 13.
G-rich sequences in DNA and RNA have a propensity to fold into stable secondary structures termed G-quadruplexes. G-quadruplex forming sequences are widespread throughout the human genome, within both, protein coding and non-coding genes, and regulatory regions. G-quadruplexes have been implicated in multiple cellular functions including chromatin epigenetic regulation, DNA recombination, transcriptional regulation of gene promoters and enhancers, and translation. Here we will review the evidence for the occurrence of G-quadruplexes both in vitro and in vivo; their role in neurological diseases including G-quadruplex-forming repeat expansions in the C9orf72 gene in frontotemporal dementia and amyotrophic lateral sclerosis and loss of the G-quadruplex binding protein FMRP in the intellectual disability fragile X syndrome. We also review mounting evidence that supports a role for G-quadruplexes in regulating the processing or function of a range of non-coding RNAs. Finally we will highlight current perspectives for therapeutic interventions that target G-quadruplexes.
DNA和RNA中富含鸟嘌呤的序列倾向于折叠成称为G-四链体的稳定二级结构。形成G-四链体的序列广泛分布于整个人类基因组中，包括蛋白质编码基因、非编码基因以及调控区域。G-四链体与多种细胞功能有关，包括染色质表观遗传调控、DNA重组、基因启动子和增强子的转录调控以及翻译。在此，我们将综述G-四链体在体外和体内出现的证据；它们在神经疾病中的作用，包括额颞叶痴呆和肌萎缩侧索硬化症中C9orf72基因形成G-四链体的重复序列扩增，以及智力障碍脆性X综合征中G-四链体结合蛋白FMRP的缺失。我们还将综述越来越多的证据，这些证据支持G-四链体在调节一系列非编码RNA的加工或功能中发挥作用。最后，我们将强调针对G-四链体的治疗干预的当前观点。
