Small-angle X-ray scattering-derived structure of the HIV-1 5′ UTR reveals 3D tRNA mimicry

Significance A highly conserved region of the HIV-1 RNA genome is responsible for regulating numerous steps of the retroviral life cycle, including initiation of reverse transcription. A complete understanding of the mechanisms controlling HIV-1 replication requires structural characterization of this RNA; unfortunately, however, its large size and conformational flexibility makes common methods of solving structures, such as X-ray crystallography and NMR, exceedingly difficult. The present study uses a solution technique, small-angle X-ray scattering coupled with computational molecular modeling, to characterize three ∼100-nucleotide RNAs that play central roles in HIV-1 replication. One of these domains mimics the L-shaped fold of tRNA, providing a structural basis for understanding how this genomic RNA coordinates interactions with a tRNA-binding host factor to facilitate initiation of reverse transcription.