Document 0865
 DOCN  M9540865
 TI    Requirement for HIV-1 TAR sequences for Tat activation in rodent cells.
 DT    9504
 AU    Sutton JA; Braddock M; Kingsman AJ; Kingsman SM; Department of
       Biochemistry, University of Oxford.
 SO    Virology. 1995 Jan 10;206(1):690-4. Unique Identifier : AIDSLINE
       MED/95133212
 AB    HIV-1 gene expression is activated via an interaction between the
       virally encoded Tat protein and a target RNA, TAR. TAR is located at the
       immediate 5' end of all viral mRNAs and comprises a partially
       base-paired stem with a tripyrimidine bulge in the upper stem and a
       hexanucleotide loop. In vitro, Tat binds specifically to the bulge and
       upper stem region with no requirement for the loop. In contrast, when
       Tat activation is analyzed in primate cells, mutations in the loop
       abolish activation, suggesting a critical role for loop binding cellular
       factors. However, in rodent cells the reverse is true. Messages with a
       mutation in the TAR loop are activated whereas messages harboring a
       wild-type TAR sequence are not activated. By testing the effect of
       mutations in the bulge and stem in the context of mutation in the loop
       we now show that this loop-independent activation by Tat in rodent cells
       requires the critical bulge-stem sequences needed for Tat binding in
       vitro. These data suggest that in rodent cells, as in vitro, Tat does
       not require a loop binding cofactor. In rodent cells containing human
       chromosome 12 (CHO12), however, Tat activation is both bulge and loop
       dependent. It appears that rodent cells, but not CHO12 cells, are
       refractory to the normal Tat/TAR activation pathway not by virtue of
       lacking a loop binding cofactor, but rather by the presence of a loop
       binding inhibitor of either Tat binding or the activation process.
 DE    Animal  Base Sequence  Chloramphenicol Acetyltransferase/GENETICS
       Chromosomes, Human, Pair 12  CHO Cells  Gene Products, tat/*METABOLISM
       Hamsters  Hela Cells  Human  *HIV Long Terminal Repeat  HIV-1/*GENETICS
       Molecular Sequence Data  Oligoribonucleotides  RNA/GENETICS/METABOLISM
       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).