title: A polycistronic transcript in transformed cells encodes the dihydrofolate reductase of herpesvirus saimiri.
abstract: Herpesvirus saimiri, an oncogenic gamma herpesvirus of primates, is the only eukaryotic virus that carries the entire metabolic gene set for a complex biochemical synthesis. Every element of the thymidine synthesis gene cascade is present in the virus, and their function is probably related to the uniquely high A + T content of the genome. Although one member of the gene set, dihydrofolate reductase (DHFR), is mapped in a region required for oncogenesis, very little is known of the expression and function of this gene in transformed cells. We report the expression of the DHFR sequence on a novel, unique tricistronic transcript in virally transformed tumor cells. The DHFR sequence is the first open reading frame on a 5.3 kb minor transcript. Alpha-amanitine sensitivity indicates that it is an RNA polymerase II transcript, and since it is also polyadenylated it appears to be a functional, relatively unstable (half-life 3 hr) mRNA. Initiation of transcription uniquely overlaps with the HSUR3 small RNA gene. Expression of the small transcript appears to be alpha-amanitine resistant, implicating polymerase III transcription. Together with the remarkably low-level expression of HSUR3 in tumor cells, the data may indicate transcription interference between two different RNA polymerases, with unusual overlapping regulation and initiation.
authors.affiliation: Department of Medical Microbiology and Immunology, University of South Florida, Tampa 33612-4799, USA.
authors.forename: S
authors.initials: S
authors.lastname: Whitaker
authors.forename: P
authors.initials: P
authors.lastname: Geck
authors.forename: M M
authors.initials: MM
authors.lastname: Medveczky
authors.forename: J
authors.initials: J
authors.lastname: Cus
authors.forename: S H
authors.initials: SH
authors.lastname: Kung
authors.forename: T
authors.initials: T
authors.lastname: Lund
authors.forename: P G
authors.initials: PG
authors.lastname: Medveczky
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D017931:DNA Primers; D004279:DNA, Viral; D015536:Down-Regulation; D006567:Herpesvirus 2, Saimiriine / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D013762:Tetrahydrofolate Dehydrogenase; D012319:RNA Polymerase II