For a long time, telomeres have been considered to be transcriptionally silent. Very recently, a breaking finding from two groups demonstrated that telomere DNA is transcribed into telomeric repeat-containing RNA in mammalian cells (Azzalin, C. M.; Reichenbach, P.; Khoriauli, L.; Giulotto, E.; Lingner, J. Science 2007, 318, 798-801. Schoefter, S.; Blasco, M. A. Nat. Cell Biol. 2008, 10, 228-236). The telomeric RNA, a newly appeared player in telomere biology, may be a key component of telomere machinery. In the current study, we used a combination of NMR, circular dichroism (CD), matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOFMS), and gel electrophoresis to investigate the structural features of a human telomere RNA sequence. We demonstrated that human telomere RNA can form a parallel G-quadruplex structure in the presence of Na(+). Importantly, we found for the first time that the G-quadruplex forming telomere RNA protects itself from enzymatic digestion. These results provide valuable information to allow understanding of the structure and function of human telomeric RNA.

Very recently, a breaking finding from two groups demonstrated that telomere DNA is transcribed into telomeric repeat-containing RNA in mammalian cells. Telomeric RNA, a newly appeared player in telomere biology, may be a key component of telomere machinery. However, structure and function of the telomeric RNA in chromosome ends have not yet been elucidated. In the current studies, we found that the human telomeric RNA sequence can form parallel G-quadruplex structure in the presence of K(+) or Na(+) ions. These results provide valuable information to allow understanding of the roles of human telomeric RNA in chromosome ends regulation and protection.

Telomeric repeat-containing RNA is a non-coding RNA molecule newly found in mammalian cells. However, structure and function of the telomeric RNA in chromosome ends have not yet been elucidated. Using a combination of NMR, CD and MALDI-TOFMS experiments, we have demonstrated that human telomere RNA can form a parallel G-quadruplex structure. Furthermore, we successfully found for the first time that human telomere DNA and RNA sequence can form a DNA-RNA hybrid type G-quadruplex structure based on click chemistry approach. Telomerase or its telomere DNA substrate is also known to present a specific target in discovering anticancer agents. Recently, we developed a structure-based approach to sequence-specific cleaving of human telomeric DNA by G-quadruplex formation. These results not only provide valuable information to allow understanding of the roles of human telomeric RNA in telomere biology, but also serve as a start step for developing new anti-cancer reagent.