Maizels Nancy, Gray Lucas T
Department of Immunology, University of Washington, Seattle, Washington, United States of America.
PLoS Genet. 2013 Apr;9(4):e1003468. doi: 10.1371/journal.pgen.1003468. Epub 2013 Apr 18.
Recent experiments provide fascinating examples of how G4 DNA and G4 RNA structures--aka quadruplexes--may contribute to normal biology and to genomic pathologies. Quadruplexes are transient and therefore difficult to identify directly in living cells, which initially caused skepticism regarding not only their biological relevance but even their existence. There is now compelling evidence for functions of some G4 motifs and the corresponding quadruplexes in essential processes, including initiation of DNA replication, telomere maintenance, regulated recombination in immune evasion and the immune response, control of gene expression, and genetic and epigenetic instability. Recognition and resolution of quadruplex structures is therefore an essential component of genome biology. We propose that G4 motifs and structures that participate in key processes compose the G4 genome, analogous to the transcriptome, proteome, or metabolome. This is a new view of the genome, which sees DNA as not only a simple alphabet but also a more complex geography. The challenge for the future is to systematically identify the G4 motifs that form quadruplexes in living cells and the features that confer on specific G4 motifs the ability to function as structural elements.
最近的实验提供了一些引人入胜的例子，展示了G4 DNA和G4 RNA结构（即四链体）如何影响正常生物学过程以及基因组病理学。四链体是短暂存在的，因此很难在活细胞中直接识别，这最初不仅引发了人们对其生物学相关性的怀疑，甚至对其是否存在也产生了质疑。现在有确凿的证据表明，一些G4基序和相应的四链体在关键过程中发挥作用，包括DNA复制起始、端粒维持、免疫逃逸和免疫反应中的调控重组、基因表达控制以及遗传和表观遗传不稳定性。因此，四链体结构的识别和解析是基因组生物学的重要组成部分。我们提出，参与关键过程的G4基序和结构构成了G4基因组，类似于转录组、蛋白质组或代谢组。这是对基因组的一种新观点，认为DNA不仅是一个简单的字母表，更是一个更复杂的版图。未来的挑战是系统地识别活细胞中形成四链体的G4基序，以及赋予特定G4基序作为结构元件发挥功能的特征。
