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J. Biol. Chem., Vol. 278, Issue 13, 11601-11611, March 28, 2003
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From the Department of Human Retrovirology, Academic Medical
Center, University of Amsterdam,
1100 DE Amsterdam, The Netherlands
The 5'-untranslated region (5'-UTR) is the most
conserved part of the HIV-1 RNA genome, and it contains regulatory
motifs that mediate various steps in the viral life cycle.
Previous work showed that the 5'-terminal 290 nucleotides of HIV-1 RNA
adopt two mutually exclusive secondary structures, long distance
interaction (LDI) and branched multiple hairpin (BMH). BMH has
multiple hairpins, including the dimer initiation signal (DIS) hairpin
that mediates RNA dimerization. LDI contains a long distance
base-pairing interaction that occludes the DIS region. Consequently,
the two conformations differ in their ability to form RNA dimers. In
this study, we have presented evidence that the full-length 5'-UTR also
adopts the LDI and BMH conformations. The downstream 290-352 region, including the Gag start codon, folds differently in the context of the
LDI and BMH structures. These nucleotides form an extended hairpin
structure in the LDI conformation, but the same sequences create a
novel long distance interaction with upstream U5 sequences in the BMH
conformation. The presence of this U5-AUG duplex was confirmed by
computer-assisted RNA structure prediction, biochemical analyses, and a
phylogenetic survey of different virus isolates. The U5-AUG
duplex may influence translation of the Gag protein because it occludes
the start codon of the Gag open reading frame.
A Novel Long Distance Base-pairing Interaction in Human
Immunodeficiency Virus Type 1 RNA Occludes the Gag Start Codon*
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Human
Retrovirology, Academic Medical Center, University of Amsterdam, P.O.
Box 22700, 1100 DE Amsterdam, The Netherlands. Tel.:
31-20-5664822; Fax: 31-20-6916531; E-mail:
b.berkhout@amc.uva.nl; Web address: www.berkhoutlab.com.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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