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Structure. 2013 Jun 4;21(6):951-62. doi: 10.1016/j.str.2013.04.008. Epub 2013 May 16.

Three-dimensional RNA structure of the major HIV-1 packaging signal region.

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Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.


HIV-1 genomic RNA has a noncoding 5' region containing sequential conserved structural motifs that control many parts of the life cycle. Very limited data exist on their three-dimensional (3D) conformation and, hence, how they work structurally. To assemble a working model, we experimentally reassessed secondary structure elements of a 240-nt region and used single-molecule distances, derived from fluorescence resonance energy transfer, between defined locations in these elements as restraints to drive folding of the secondary structure into a 3D model with an estimated resolution below 10 Å. The folded 3D model satisfying the data is consensual with short nuclear-magnetic-resonance-solved regions and reveals previously unpredicted motifs, offering insight into earlier functional assays. It is a 3D representation of this entire region, with implications for RNA dimerization and protein binding during regulatory steps. The structural information of this highly conserved region of the virus has the potential to reveal promising therapeutic targets.

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