The long range goal of my research is to study the regulation of gene expression of DNA tumor virus genomes and use this knowledge to understand the mechanism of eukaryotic gene experession and virus-host cell interactions. The principles governing the molecular basis of regulatory controls in eukaryotes are far from clear. DNA tumor viruses replicate in animal cell nuclei and their genes are regulated in eukaryotic cellular environment. Therefore, they provide a challenging model system to study the control of eukaryotic gene expression. Specifically, we propose to study three aspects of adenovirus type 5 gene expression during the tenure of the proposed grant. They are: (1) Mutational analysis of DNA sequences involved in the promotor function of early transcriptional region 2 (E-2A) early and late promotors at the level of viral chromosome and to study the relationship between the regulation of transcription from the two E-2A promotors and E1-A gene products using an SV40 host-vector system. (2) Identify and analyze in vivo, the RNA polymerase II transcriptional termination signals using Ad2 major late transcription unit as a model system. (3) In the future, we propose to continue our DNA tumor virus studies and attempt to identify the role of tripartite leader segments of adenoviral late mRNAs in their biogenesis and translation.
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