Structure, function and targeting of human telomere RNA

Abstract

Human telomeres play an important role in critical processes underlying genome stability, cancer, and aging. For a long time, telomeres have been considered transcriptionally silent. A recent finding demonstrated that telomere DNA is transcribed into telomeric repeat-containing RNA (referred to as TERRA) in mammalian cells. The existence of TERRA RNA may reveal a new level of regulation and protection of chromosome ends that could promote valuable insight into fundamental biological processes such as cancer and aging. Revealing the structure and function of telomere RNA will be essential for understanding telomere biology and telomere-related diseases. NMR and X-ray crystallography have demonstrated that human telomere RNA forms G-quadruplex structures. More recently, human telomere RNA is suggested to form a G-quadruplex dimer in the living cells by employing a light-switching probe. The proposed structures may be a valuable target for anticancer agents directed against telomeres.This review highlights the structures and topologies for telomere RNA G-quadruplex and recent efforts in the design of telomere RNA G-quadruplex ligands. The future challenges in the field are outlined.