Project Details


DESCRIPTION (adapted from investigator's abstract): HIV encodes a novel
regulatory protein, (Tat), which is important for virus growth,
pathogenesis and latency. It encodes a transacting stimulator of HIV
gene expression. A cis acting element called TAR, located in the long
terminal repeat (LTR), downstream of the transcription initiation site
in the provirus, is required for transactivation by Tat. The mechanism
whereby Tat stimulates HIV gene expression remains uncertain. It is
generally accepted that its major action is at the level of
transcription, although the extent to which the stimulation is due to
effects on transcriptional initiation or elongation is still unresolved.
However, it is well-established that Tat can stimulate at the elongation
level, both in vivo and in vitro. The present proposal is based on the
hypothesis that transcription complexes formed at the HIV promoter in the
absence of Tat are unstable during elongation and that TAR RNA forms a
scaffold for the binding of Tat and of cellular proteins which alter the
complexes so as to increase their elongational competence. The principal
objective of the proposed collaboration is to explore the mechanism
underlying this process and to discover the identity of the
transcription factor(s) that are recruited into the complex by Tat and
TAR. To this end, the project will exploit in vitro transcription
systems of three types; (i) a conventional HeLa cell nuclear extract
that responds to Tat, (ii) a system in which the DNA template is
immobilized on agarose beads so that components can be added and removed
at will, and (iii) a system directed by templates carrying heterologous
attenuator signals that can cause polymerase pausing and termination.
Effective start/end date9/30/949/29/97


  • Fogarty International Center
  • Fogarty International Center


  • Genetics
  • Molecular Biology


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