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).