Nucleic Acids Research, Vol 25, Issue 14 2902-2910, Copyright © 1997 by Oxford University Press
MA Lochrie, S Waugh, DG Pratt Jr, J Clever, TG Parslow and B Polisky
RNA ligands that bind to the human immunodeficiency virus type-1 (HIV- 1)
gag polyprotein with 10(-9) M affinity were isolated from a complex pool of
RNAs using an in vitro selection method. The ligands bind to two different
regions within gag, either to the matrix protein or to the nucleocapsid
protein. Binding of a matrix ligand to gag did not interfere with the
binding of a nucleocapsid ligand, and binding of a nucleocapsid ligand to
gag did not interfere with the binding of a matrix ligand. However, binding
of a nucleocapsid ligand to gag did interfere with binding of an RNA
containing the HIV-1 RNA packaging element (psi), even though the sequence
of the nucleocapsid ligand is not similar topsi. The minimal sequences
required for the ligands to bind to matrix or nucleocapsid were determined.
Minimal nucleocapsid ligands are predicted to form a stem-loop structure
that has a self- complementary sequence at one end. Minimal matrix ligands
are predicted to form a different stem-loop structure that has a CAARU loop
sequence. The properties of these RNA ligands may provide tools for
studying RNA interactions with matrix and nucleocapsid, and a novel method
for inhibiting HIV replication.
ARTICLES
In vitro selection of RNAs that bind to the human immunodeficiency virus type-1 gag polyprotein
NeXstar Pharmaceuticals, Inc., 2860 Wilderness Place, Boulder, CO 80301, USA. mlochrie@nexstar.com
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