The 5’ untranslated region (5’-UTR) is a highly conserved region of retroviral RNA genomes responsible for regulating many steps of the retroviral lifecycle including viral RNA dimerization, packaging, initiation of reverse transcription, transcriptional regulation, and splicing. A complete understanding of the mechanisms controlling retroviral replication requires structural characterization of this RNA. Unfortunately, its large size and conformational flexibility renders common methods of solving structures, such as X-ray crystallography and NMR exceedingly difficult. Here, we use a solution technique, small-angle X-ray scattering (SAXS), coupled with computational molecular modeling and structure probing, to characterize RNAs (100-350 nucleotides in length) derived from the 5’-UTR of HIV-1 and other retroviruses. Similarities and differences in their packaging signals, the presence of tRNA structural mimicry, conformational switches upon dimerization and primer annealing, and length-dependent changes in global conformation will all be discussed.
