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Looking at HIV-1 RNA Dimerization Initiation

During retrovirus assembly, two identical copies of genomic RNA are packaged into the viral particles. This non-covalently linked dimer of RNA is important for various critical events in the viral life cycle, including reverse transcription, recombination, RNA packaging, and viral infectivity. The packaging signal for the RNA is located in the 5'-untranslated region of unspliced RNA, which contains four stem-loop structures, SL1, SL2, SL3, and SL4. SL1, a 35-nucleotide hairpin, serves as the dimerization initiation site and spontaneously dimerizes via a palindromic hexanucleotide sequence in its apical loop. SL1 also contains a conserved G-rich 1–3 internal loop (G-bulge) that is important for packaging and overall infectivity. Several structures of short SL1 RNA constructs have been solved, but no model of the full-length SL1 RNA exists.

The structure of HIV SL1.

In this Paper of the Week, Nikolai B. Ulyanov and colleagues present the NMR structure of the full-length linear dimer of SL1 from HIV-1. The structure was refined using nuclear Overhauser effect and residual dipolar coupling data. Ulyanov et al. found that although the G-bulges display high conformational variability, most conformations contain two exposed guanines that may be recognized by the nucleocapsid protein, which binds tightly to the G-bulge in vitro. Determination of this SL1 structure is important for understanding dimerization and packaging of retroviral RNA and is potentially valuable for structure-based development of therapeutic drugs that interfere with these processes in HIV-1.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 16168–16177

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