Nucleic Acids Research, 2001, Vol. 29, No. 12 2594-2600
© 2001 Oxford University Press
Mutations in the TAR hairpin affect the equilibrium between alternative conformations of the HIV-1 leader RNA
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
The HIV-1 untranslated leader RNA can adopt two mutually exclusive conformations that represent alternative secondary structures. This leader RNA can fold either an extended duplex through long-distance base pairing or a branched conformation in which the RNA locally folds into hairpin structures. Both leader RNA conformations have the TAR hairpin in common, which forms the extreme 5' end of all HIV-1 transcripts. We report that truncation of the TAR hairpin shifts the equilibrium between the two RNA conformations away from the thermodynamically favored long-distance interaction. However, the equilibrium is partially restored in response to the cations Na+ and Mg2+. The transcripts with mutant TAR structures allowed us to investigate conditions affecting the competition between the alternative conformations of the HIV-1 leader RNA. We also demonstrate that the change in conformation of the leader RNA due to TAR truncations severely affects formation of the HIV-1 RNA dimer.
* To whom correspondence should be addressed. Tel: +31 20 566 4822; Fax: +31 20 691 6531; Email: b.berkhout{at}amc.uva.nl
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