A comparison of DNA and RNA quadruplex structures and stabilities

Abstract

Guanosine-rich sequences are prone to fold into four-stranded nucleic acid structures. Such quadruplex sequences have long been suspected to play important roles in regulatory processes within cells. Although DNA quadruplexes have been studied in great detail, four-stranded structures made up from RNA have received only minor attention, although it is known that RNA is able to form stable quadruplexes as well. Here, we compare quadruplex structures and stabilities of a variety of DNA and RNA sequences. We focus on well established DNA sequences and determine the topologies and stabilities of the corresponding RNA sequences by CD spectroscopy and CD thermal melting experiments. We find that the RNA sequences exclusively fold into the all-parallel conformation in contrast to the diverse topologies adopted by DNA quadruplexes. The thermal stabilities of the RNA structures rival those of the corresponding DNA sequences, often displaying enhanced stabilities compared to their DNA counterparts. Especially thermodynamically less stable sequences show a strong preference for potassium, with the RNA quadruplexes exhibiting much higher stabilities than the corresponding DNAs. The latter finding suggests that quadruplexes formed at critical positions in mRNAs might perturb gene expression to a larger extend than previously anticipated.