Portability of a Common Nucleic Acid Hairpin Loop Motif Between RNA and DNA

Abstract

Hairpins are common nucleic acid secondary structures that perform both structural and functional roles. Recently, we reported that r(UNCG) and r(GNRA) hairpin families use molecular mimicry and electrostatic factors to attain exceptional thermodynamic stability with a CG closing base pair (cbp) (J. Amer. Soc. 2009 131, 8474-8484). Although these loop families fold with different global structures, the tetraloops are stabilized by displaying the same functional groups and partial charges to the major groove edge of the CG cbp. Herein, we compare the r(GNRA) tetraloop family to the DNA triloop family d(GNA), which is also exceptionally stable with a CG cbp and possesses same sheared GA base pair between the first and last positions of the loop (Biochemistry2009 48, 8787-8794). Interactions of d(GNA) loops with the cbp were probed with nucleobase and functional group modifications and the resulting effects on stability were compared to those from similar substitutions in r(GNRA) hairpins. Interruption or deletion of loop-cbp interactions in d(GNA) was consistent with electrostatic interactions identified through nonlinear Poisson-Boltzmann (NLPB) calculations. Moreover, loop stability changed in a manner consistent with similar loop-cbp interactions for d(GNA) and r(GNRA) loops. We also compared the relationship of ΔG°37 and log[Na+] for d(GNA) and r(GNRA) loops and found a decreased salt dependence for both loop families with a CG cbp. Similarity of loop-cbp interactions shows portability of the loop-cbp motif across polymer type and loop size and indicates RNA and DNA converged on a similar molecular solution for stability.