Oligonucleotide Models of Telomeric DNA and RNA Form a Hybrid G-quadruplex Structure as a Potential Component of Telomeres
Oligonucleotide Models of Telomeric DNA and RNA Form a Hybrid G-quadruplex Structure as a Potential Component of Telomeres
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DOI：
10.1074/jbc.m112.342030
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发表时间：
2012-12-07
影响因子：
4.8
通讯作者：
Hayashi, Tetsuya
中科院分区：
文献类型：
--
作者：
Xu, Yan;Ishizuka, Takumi;Hayashi, Tetsuya
含有端粒重复序列的RNA是最近在哺乳动物细胞中发现的一种非编码RNA分子。尽管端粒RNA分子可能是端粒机制的关键组成部分，但其在人类染色体末端的详细结构特征和功能仍不清楚。在这项研究中，使用模型人类端粒DNA和RNA序列，我们证明了人类端粒RNA和DNA寡核苷酸形成DNA-RNA G-四链体。接下来，我们采用基于化学的寡核苷酸探针来模拟活细胞中天然形成的端粒DNA-RNA G-四链体，这表明端粒DNA和RNA的寡核苷酸模型的DNA-RNA G-四链体形成过程可以在细胞中发生。此外，我们研究了这种DNA-RNA G-四链体的可能作用。DNA-RNA G-四链体的形成导致细胞克隆能力显着增加，并对抑制细胞衰老有作用。在这里，我们已经使用了一个模型系统，以提供证据的G-四链体结构的形成，涉及端粒DNA和RNA序列，有可能提供一个保护性的端粒末端加帽结构。
Telomeric repeat-containing RNA, a non-coding RNA molecule, has recently been found in mammalian cells. The detailed structural features and functions of the telomeric RNA at human chromosome ends remain unclear, although this RNA molecule may be a key component of the telomere machinery. In this study, using model human telomeric DNA and RNA sequences, we demonstrated that human telomeric RNA and DNA oligonucleotides form a DNA-RNA G-quadruplex. We next employed chemistry-based oligonucleotide probes to mimic the naturally formed telomeric DNA-RNA G-quadruplexes in living cells, suggesting that the process of DNA-RNA G-quadruplex formation with oligonucleotide models of telomeric DNA and RNA could occur in cells. Furthermore, we investigated the possible roles of this DNA-RNA G-quadruplex. The formation of the DNA-RNA G-quadruplex causes a significant increase in the clonogenic capacity of cells and has an effect on inhibition of cellular senescence. Here, we have used a model system to provide evidence about the formation of G-quadruplex structures involving telomeric DNA and RNA sequences that have the potential to provide a protective capping structure for telomere ends.