Intrinsic conformational dynamics of the HIV-1 genomic RNA 5′UTR

Significance Here we have directly visualized conformational changes in the 5′UTR of the HIV-1 genome using single-molecule fluorescence techniques. We find that the monomeric 5′UTR can spontaneously transition between two conformations, which have distinct intramolecular base pairing. One of the observed conformations is competent for dimerization with a second 5′UTR molecule. Our results are consistent with a model in which dimerization initiates by way of localized intermolecular kissing-loop base pairing, which is promoted by tRNA primer annealing. The intermolecular interface then extends, giving rise to the putative extended dimer, which is stabilized by HIV-1 NC. Thus, the 5′UTR is intrinsically dynamic, and both viral and host factors play a role in modulating the RNA conformation and dynamics.