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.

RNA Lego: The use of natural riboswitch aptamers in synthetic RNA switches (see picture) should broaden the scope of artificial RNA regulators dramatically. It is shown that thiamine pyrophosphate (TPP) aptamers can be used in engineered devices as very sensitive switches of gene expression in unmodified organisms. The approach demonstrates that intrinsic metabolites can be utilized as external effectors of cellular functions.

Quadruple alliance: By performing a screen for binders of the human telomeric repeat sequence with small molecule libraries, the principle of which is outlined in the scheme, we have identified novel compounds that stabilise the G quadruplex structure. Some of these could be suitable leads for further optimisation as potent and selective quadruplex ligands.

RNA‐Lego: Die Verwendung von natürlichen RNA‐Schalter‐Aptameren in synthetischen RNA‐Schaltern (siehe Bild) dürfte die Bandbreite künstlicher RNA‐Regulatoren enorm vergrößern. Es wird gezeigt, dass Thiaminpyrophosphat‐Aptamere in gentechnisch veränderten Funktionseinheiten als hochempfindliche Schalter der Genexpression in nichtmodifizierten Organismen eingesetzt werden können. Der Ansatz illustriert, dass intrinsische Metabolite als externe Effektoren zellulärer Funktionen nutzbar sind.magnified image

The utilization of toehold-containing DNA strands allows for the assembly of complex nanostructures via kinetically driven hybridization reactions. Here, we have rendered this strategy ligand-dependent, resulting in small-molecule-inducible DNA nanoarchitectures.