Kiliszek Agnieszka, Rypniewski Wojciech
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland
Nucleic Acids Res. 2014 Jul;42(13):8189-99. doi: 10.1093/nar/gku536. Epub 2014 Jun 17.
CNG repeats (where N denotes one of the four natural nucleotides) are abundant in the human genome. Their tendency to undergo expansion can lead to hereditary diseases known as TREDs (trinucleotide repeat expansion disorders). The toxic factor can be protein, if the abnormal gene is expressed, or the gene transcript, or both. The gene transcripts have attracted much attention in the biomedical community, but their molecular structures have only recently been investigated. Model RNA molecules comprising CNG repeats fold into long hairpins whose stems generally conform to an A-type helix, in which the non-canonical N-N pairs are flanked by C-G and G-C pairs. Each homobasic pair is accommodated in the helical context in a unique manner, with consequences for the local helical parameters, solvent structure, electrostatic potential and potential to interact with ligands. The detailed three-dimensional profiles of RNA CNG repeats can be used in screening of compound libraries for potential therapeutics and in structure-based drug design. Here is a brief survey of the CNG structures published to date.
CNG重复序列(其中N代表四种天然核苷酸之一)在人类基因组中大量存在。它们发生扩增的倾向会导致被称为三核苷酸重复扩增疾病(TREDs)的遗传性疾病。如果异常基因得以表达,毒性因子可能是蛋白质,也可能是基因转录本,或者两者皆是。基因转录本在生物医学界备受关注,但其分子结构直到最近才得到研究。包含CNG重复序列的模型RNA分子折叠成长发夹结构,其茎通常符合A型螺旋,其中非经典的N-N碱基对两侧是C-G和G-C碱基对。每个同碱基对以独特的方式容纳在螺旋环境中,这对局部螺旋参数、溶剂结构、静电势以及与配体相互作用的潜力都会产生影响。RNA CNG重复序列的详细三维结构可用于筛选化合物文库以寻找潜在疗法,以及用于基于结构的药物设计。以下是对迄今为止已发表的CNG结构的简要综述。