Follow the Leader

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Science  14 Oct 2011:
Vol. 334, Issue 6053, pp. 155
DOI: 10.1126/science.334.6053.155-h

The 5′-leader of the HIV RNA genome regulates multiple steps in HIV replication, however, an understanding of the mechanism has been hindered by lack of structural information. Lu et al. (p. 242) used a nuclear magnetic resonance labeling strategy to probe structural elements in both monomeric and dimeric forms of an RNA sequence comprising the entire 5′-untranslated region (335 nucleotides) and 21 nucleotides of the coding sequence. A conformational switch associated with long-range base-pairing was identified that regulates whether the genome is packaged or translated. One conformation sequestered the start codon, but promoted dimerization and binding to the viral nucleocapsid protein to mediate packaging, while the second sequestered the sequence that promotes dimerization, allowing for translation of the viral RNA.

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