Molecular basis of human telomere DNA/RNA structure and its potential application.

Abstract

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.