Unusual regulation of simian virus 40 early-region transcription in genomes containing two origins of DNA replication.
As part of our efforts to create multifunctional vectors for the transduction of animal cells, a set of simian virus 40 recombinants were constructed which contain an inverted duplication of the region including the origin of viral DNA replication (ori) and the early-region promoter. The unusual aspects of the structure of these recombinant genomes revealed several unexpected features of their function. In particular, transcription from the early-region promoters on these recombinants occurred primarily after the start of DNA replication, and, in that sense, these promoters behaved as if they were late-region promoters. This behavior results from the fact that these genomes contain multiple ori segments, and, therefore, they replicate earlier and faster than wild-type virus DNA, thereby causing a precocious shift in the initiation of early-region transcription from sites downstream of ori to sites located upstream of ori. The abnormal expression from multiple ori genomes is consistent with our present notions regarding the replication-dependent shift in early-region transcriptional start sites (Buchman et al., Mol. Cell. Biol. 4:1900-1914). Since our experiments demonstrate that RNAs initiated upstream of ori contribute to T-antigen formation late in infection, we suggest that the shift in early-region transcription starts modulates large T-antigen production in concert with viral DNA replication.
D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D004261:DNA Replication; D004262:DNA Restriction Enzymes; D005786:Gene Expression Regulation; D005796:Genes; D005814:Genes, Viral; D005914:Globins / Q000235:genetics; D007668:Kidney; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D011817:Rabbits; D013539:Simian virus 40 / Q000235:genetics*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D012367:RNA, Viral; D014764:Viral Proteins; D005914:Globins; D011494:Protein Kinases; D004262:DNA Restriction Enzymes