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Nucleic Acids Research Advance Access originally published online on December 20, 2007
Nucleic Acids Research 2008 36(4):1098-1112; doi:10.1093/nar/gkm1083
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Nucleic Acids Research, 2008, Vol. 36, No. 4 1098-1112
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Structural Biology

Loop dependence of the stability and dynamics of nucleic acid hairpins

Serguei V. Kuznetsov1, Cha-Chi Ren2, Sarah A. Woodson2 and Anjum Ansari1,3,*

1Department of Physics (M/C 273), University of Illinois at Chicago, 845 W. Taylor St., Chicago, IL 60607, 2Department of Biophysics, Johns Hopkins University, 3400 N. Charles St, Baltimore, MD 21218-2685 and 3Department of Bioengineering (M/C 063), University of Illinois at Chicago, 845 W. Taylor St., Chicago, IL 60607, USA

*To whom correspondence should be addressed. Tel: +312 996 8735; Fax: +312 996 9016; Email: ansari{at}uic.edu

Received June 19, 2007. Revised November 6, 2007. Accepted November 19, 2007.

Hairpin loops are critical to the formation of nucleic acid secondary structure, and to their function. Previous studies revealed a steep dependence of single-stranded DNA (ssDNA) hairpin stability with length of the loop (L) as ~L8.5 ± 0.5, in 100 mM NaCl, which was attributed to intraloop stacking interactions. In this article, the loop-size dependence of RNA hairpin stabilities and their folding/unfolding kinetics were monitored with laser temperature-jump spectroscopy. Our results suggest that similar mechanisms stabilize small ssDNA and RNA loops, and show that salt contributes significantly to the dependence of hairpin stability on loop size. In 2.5 mM MgCl2, the stabilities of both ssDNA and RNA hairpins scale as ~L4 ± 0.5, indicating that the intraloop interactions are weaker in the presence of Mg2+. Interestingly, the folding times for ssDNA hairpins (in 100 mM NaCl) and RNA hairpins (in 2.5 mM MgCl2) are similar despite differences in the salt conditions and the stem sequence, and increase similarly with loop size, ~L2.2 ± 0.5 and ~L2.6 ± 0.5, respectively. These results suggest that hairpins with small loops may be specifically stabilized by interactions of the Na+ ions with the loops. The results also reinforce the idea that folding times are dominated by an entropic search for the correct nucleating conformation.


Present address: Cha-Chi Ren, DC Public Schools, 825 N. Capitol St, Washington D.C. 20036, USA


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