The use of animal viruses as model systems for probing the complexities of molecular control mechanisms has been particularly fruitful. It is generally thought that understanding of genetic regulation in viruses will provide an insight into similar processes in eukaryotic cells. The overall objective of our research is to systematically develop our understanding of gene regulation in virus infected cells and to use this knowledge for developing in vitro systems from which activities can be purified and characterized. In the present renewed application we specifically intend to accomplish the following: 1) To characterize the structure of the actively transcribed viral minichromosomes and the role of minichromosome associated proteins in the regulation of transcription. 2) To test and substantiate our recently published model (Hay, N., Skolnik-David, H. and Aloni, Y. Cell 29, 183-193, 1982) for quantitative regulation of the synthesis of SV40 capsid proteins by attenuation and mRNA modulation in a feedback control mechanism. 3) To determine the role of the nuclear matrix and cytoskeleton in virus assembly and in the biogenesis of viral RNA. 4) To study the mechanism of transcription-termination, RNA processing, polyadenylation and splicing. The acquisition of knowledge by the present research will ultimately contribute to a better understanding of the more complex phenomena in mammalian cells, such as molecular process of differentiation, development and malignant transformation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA014995-12
Application #
3164060
Study Section
Virology Study Section (VR)
Project Start
1977-03-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Weizmann Institute of Science
Department
Type
DUNS #
City
Rehovot
State
Country
Israel
Zip Code
76100
Shor, J; Ben-Asher, E; Aloni, Y (1995) Transcription elongation of the murine ornithine decarboxylase (ODC) gene is regulated in vitro at two downstream elements by different attenuation mechanisms. Oncogene 10:1587-96
Ori, A; Shaul, Y (1995) Hepatitis B virus enhancer binds and is activated by the Hepatocyte nuclear factor 3. Virology 207:98-106
Krauskopf, A; Aloni, Y (1994) A cellular repressor regulates transcription initiation from the minute virus of mice P38 promoter. Nucleic Acids Res 22:828-34
Krauskopf, A; Ben-Asher, E; Aloni, Y (1994) Minute virus of mice infection modifies cellular transcription elongation. J Virol 68:2741-5
Levine, A; Yeivin, A; Ben-Asher, E et al. (1993) Histone H1-mediated inhibition of transcription initiation of methylated templates in vitro. J Biol Chem 268:21754-9
Usheva, A; Maldonado, E; Goldring, A et al. (1992) Specific interaction between the nonphosphorylated form of RNA polymerase II and the TATA-binding protein. Cell 69:871-81
Goldring, N B; Kessler, M; Aloni, Y (1992) Parameters affecting the elongation block by RNA polymerase II at the SV40 attenuator 1 in vitro. Biochemistry 31:8369-76
Resnekov, O; Pruzan, R; Aloni, Y (1991) Elements involved in an in vitro block to transcription elongation at the end of the L1 mRNA family of adenovirus 2. Nucleic Acids Res 19:1783-90
Bengal, E; Flores, O; Krauskopf, A et al. (1991) Role of the mammalian transcription factors IIF, IIS, and IIX during elongation by RNA polymerase II. Mol Cell Biol 11:1195-206
Krauskopf, A; Bengal, E; Aloni, Y (1991) The block to transcription elongation at the minute virus of mice attenuator is regulated by cellular elongation factors. Mol Cell Biol 11:3515-21

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