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M94A0219.TXT
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1994-10-08
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Document 0219
DOCN M94A0219
TI Identification of a novel HIV-1 TAR RNA bulge binding protein.
DT 9412
AU Baker B; Muckenthaler M; Vives E; Blanchard A; Braddock M; Nacken W;
Kingsman AJ; Kingsman SM; Glaxo Group Research and Development Ltd,
Greenford, Middlesex,; UK.
SO Nucleic Acids Res. 1994 Aug 25;22(16):3365-72. Unique Identifier :
AIDSLINE MED/94359809
AB The Tat protein binds to TAR RNA to stimulate the expression of the
human immunodeficiency virus type 1 (HIV-1) genome. Tat is an 86 amino
acid protein that contains a short region of basic residues (aa49-aa57)
that are required for RNA binding and TAR is a 59 nucleotide stem-loop
with a tripyrimidine bulge in the upper stem. TAR is located at the 5'
end of all viral RNAs. In vitro, Tat specifically interacts with TAR by
recognising the sequence of the bulge and upper stem, with no
requirement for the loop. However, in vivo the loop sequence is critical
for activation, implying a requirement for accessory cellular TAR RNA
binding factors. A number of TAR binding cellular factors have been
identified in cell extracts and various models for the function of these
factors have been suggested, including roles as coactivators and
inhibitors. We have now identified a novel 38 kD cellular factor that
has little general, single-stranded or double-stranded RNA binding
activity, but that specifically recognises the bulge and upper stem
region of TAR. The protein, referred to as BBP (bulge binding protein),
is conserved in mammalian and amphibian cells and in Schizosaccharomyces
pombe but is not found in Saccharomyces cerevisiae. BBP is an effective
competitive inhibitor of Tat binding to TAR in vitro. Our data suggest
that the bulge-stem recognition motif in TAR is used to mediate cellular
factor/RNA interactions and indicates that Tat action might be inhibited
by such competing reactions in vivo.
DE Animal Base Sequence Binding Sites Binding, Competitive Cell
Nucleus/CHEMISTRY CHO Cells Factor Xa/METABOLISM Gene Products,
tat/*METABOLISM Hamsters Hela Cells Human HIV-1/*GENETICS Molecular
Sequence Data Nucleic Acid Conformation Peptide Fragments/METABOLISM
RNA-Binding Proteins/*ANALYSIS/CHEMISTRY/METABOLISM RNA,
Viral/CHEMISTRY/*METABOLISM Species Specificity Structure-Activity
Relationship Support, Non-U.S. Gov't JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).