Formation of a Stacked Dimeric G-Quadruplex Containing Bulges by the 5′-Terminal Region of Human Telomerase RNA (hTERC)

We investigate the structure formed by the first 18-nt of the 5′-terminal region of the human telomerase RNA (hTERC or hTR) using gel electrophoresis and UV, CD, and NMR spectroscopy. Our data suggest that this 18-nt sequence, r(GGGUUGCGGAGGGUGGGC), can form a stacked dimeric G-quadruplex in potassium solution. The two subunits, each being a three-layer parallel-stranded G-quadruplex with a cytosine bulge, are stacked at their 5′-end. The formation of this stacked dimeric G-quadruplex containing bulges could be biologically relevant for the dimerization and other interactions of the active human telomerase.