Project: Research project

Project Details


We have obtained preliminary data that an element exists within the 5' 32
nucleotides of the R components of the genomes of certain murine leukemia
viruses (MuLVs) that contributes to the transcriptional activity of the
virus. The R regions of the MuLVs, which are situated downstream of the
initiation site of the transcription, bear striking similarity to those
of the gibbon ape leukemia virus, simian sarcoma virus, and feline
leukemia viruses. Our preliminary data indicate that secondary structure
of the R sequences is important for the activity of the element. Also,
the R region element acts at least in part to increase RNA polymerase II
loading onto viral LTR templates, as detected in nuclear run-on assays.
We propose here to perform a detailed series of studies to investigate
how the MuLV element functions. In particular, we hypothesize that the
MuLV R region element functions in a manner analogous to that of the
HIV-1 TAR element. Specifically, we hypothesize that a cellular factor
exists that is functionally equivalent to HIV-1 Tat and recognizes the
MuLV R element at the level of RNA to stimulate transcriptional
initiation and/or RNA polymerase processivity. We propose to use a
mutagenesis approach to identify precisely which nucleotides within the
MuLV R element are critical for activity. A series of experiments will
be performed to test whether the MuLV sequences function as a DNA or RNA
moiety. We will also determine whether they strictly affect
transcriptional initiation or whether they affect processivity of RNA
polymerase molecules loaded onto viral transcriptional templates. other
viruses will be examined to see whether they contain a similar element
and what the sequence context requirements for the function of the MuLV
element are. We will also test whether the MuLV sequence can at least
partially substitute for the HIV-1 TAR element. Protein-nucleic acid
binding assays will be used to look for cellular factors that recognize
the MuLV R region element.
Effective start/end date7/1/922/28/98


  • Oncology
  • Cancer Research


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