Unusual Topological RNA Architecture with an Eight-Stranded Helical Fragment Containing A‑, G‑, and U‑Tetrads

Human telomeric RNA performs various cellular functions such as telomere length regulation, heterochromatin formation, and chromosome end protection. Using a combination of nuclear magnetic resonance, circular dichroism, and gel electrophoresis, we observed an unusual topological structure formed by human telomere RNA r­(GUUAGGGU). Our results showed that every set of four strands formed a parallel G-quadruplex as symmetry-related units containing four G-tetrads, two U-tetrads, and one A-tetrad. An eight-stranded helical fragment containing A-, G-, and U-tetrads provided a central intercalated scaffold that connected two G-quadruplex units in an alternating antiparallel arrangement, giving rise to a novel RNA architecture. This higher order RNA structure is so stable that it would be surprising if similar structures do not occur in nature. Our findings provide a new insight into the behavior of human telomeric RNA molecules.