title: Finding a human telomere DNA-RNA hybrid G-quadruplex formed by human telomeric 6-mer RNA and 16-mer DNA using click chemistry: a protective structure for telomere end.
abstract: Telomeric repeat-containing RNA is a non-coding RNA molecule newly found in mammalian cells. The telomere RNA has been found to localize to the telomere DNA, but how the newly discovered RNA molecule interacts with telomere DNA is less known. In this study, using the click chemistry we successfully found that a 6-mer human telomere RNA and 16-mer human telomere DNA sequence can form a DNA-RNA hybrid type G-quadruplex structure. Detection of the click-reaction products directly probes DNA-RNA G-quadruplex structures in a complicated solution, whereas traditional methods such as NMR and crystallography may not be suitable. Importantly, we found that formation of DNA-RNA G-quadruplex induced an exonuclease resistance for telomere DNA, indicating that such structures might be important for protecting telomeric DNA from enzyme digestion to avoid telomere DNA shortening. These results provide the direct evidence for formation of DNA-RNA hybrid G-quadruplex structure by human telomere DNA and RNA sequence, suggesting DNA-RNA hybrid G-quadruplex structure associated between telomere DNA and RNA may respond to chromosome end protection and/or present a valuable target for drug design.
authors.affiliation: Division of Chemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. Electronic address: xuyan@fc.miyazaki-u.ac.jp.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku 153-8904, Tokyo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Chemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Ishizuka
authors.affiliation: Division of Chemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Chao-Da
authors.initials: CD
authors.lastname: Xiao
authors.affiliation: Division of Chemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Microbial Genomics, Department of Genomics and Bioenvironmental Science, Frontier Science Research Center, Faculty of Medicine, University of Miyazaki, 5200 Kiyotake, Miyazaki 889-1692, Japan; Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku 153-8904, Tokyo, Japan; Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan. Electronic address: komiyama@tara.tsukuba.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Komiyama
mesh_terms: D057930:Click Chemistry; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry*
chemical_list: D012313:RNA; D004247:DNA
keywords: Click chemistry; G-quadruplex; Human telomere RNA