Key result
TAR hairpin truncation shifts HIV-1 leader RNA equilibrium and severely impairs RNA dimer formation.
Why the study?
The equilibrium between alternative conformations of the HIV-1 leader RNA and the role of the TAR hairpin in this process were not fully understood.
Truncation of the TAR hairpin alters the conformational equilibrium of the HIV-1 leader RNA and impairs RNA dimer formation.
TAR integrity is required for HIV-1 RNA dimerization; leaves open whether this motif is a viable target for future antivirals.
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 Mg(2+). 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.
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Hendrik Huthoff (2001) studied HIV-1. Truncation of the TAR hairpin vs. Wild-type TAR structures was evaluated on Equilibrium between alternative conformations of the HIV-1 leader RNA and RNA dimer formation. Truncation of the TAR hairpin shifted the equilibrium of HIV-1 leader RNA conformations away from the long-distance interaction and severely affected formation of the HIV-1 RNA dimer.
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