NMR detection of intermolecular interaction sites in the dimeric 5′-leader of the HIV-1 genome

Significance A nucleotide-specific 2 H-edited NMR approach was used to determine the nature of the intermolecular interface in the intact, dimeric HIV type-1 (HIV-1) 5′-leader RNA (230 kD). The studies distinguish between previously proposed extended duplex and kissing hairpin models and identify additional intermolecular interaction sites. A one-dimensional 2 H-edited NMR method that allows temporal monitoring of intermolecular base-pair formation revealed that the observed “extended dimer interface” forms rapidly, even in the absence of RNA chaperones. In addition to addressing long-standing questions about retroviral genome dimerization, these studies illustrate the utility of 2 H-edited NMR for determining the structures and folding kinetics of relatively large RNAs.