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Updated: Nov 13, 2025

Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
HIV-1 genomic RNA U3 region forms a stable quadruplex-hairpin structure
Chelsea Harpster1, Elaina Boyle1, Karin Musier-Forsyth1
1Department of Chemistry and Biochemistry, Center for Retroviral Research and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
Abstract:
The U3 promoter region of the HIV-1 long terminal repeat (LTR) has previously been shown to fold into a series of dynamic G-quadruplex structures. Among the G-quadruplexes identified in the LTR sequence, LTR-III was shown to be the most stable in vitro. NMR studies of this 28-nucleotide (nt) DNA revealed a unique quadruplex-hairpin structure. Whether the hairpin forms in RNA element is unknown and the role of the hairpin in the structure and stability of quadruplexes has not been characterized. Here, we used optical and thermodynamic studies to address these questions. The wild-type LTR-III RNA formed a monomolecular quadruplex with a parallel topology using only propeller loops, including the hairpin loop element. By comparison to the WT and variant RNAs, LTR-III DNA structures were more heterogeneous and less stable. Increased stability of the RNA suggests that the RNA quadruplex-hairpin structure may be a more attractive therapeutic target than the analogous DNA element.
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