Post-transcriptional control of avian oncornavirus transforming gene sequences in mammalian cells

Abstract

TRANSFORMATION of cells by RNA tumour viruses generally results in a stable association of the viral genome with the morphologically altered cell. Studies with temperature-sensitive mutants of these viruses have clearly demonstrated that viral-specific gene functions are required for establishment and maintenance of the transformed phenotype^1–6. For avian oncornaviruses the transforming (sarcoma) gene sequences are required for both transformation of cells in tissue culture and the production of tumours in animals^7–8. In all of the oncornavirus-infected mammalian cell systems studied to date regulation of expression of the avian RNA tumour virus transforming gene sequences seems to be under the influence of transcriptional control mechanism(s) because appreciable differences in the amount of sarcoma-specific RNA can be detected in cells exhibiting normal and transformed phenotypes. For instance, the amount of sarcoma-specific RNA was substantially reduced in most revertant subclones of Rous sarcoma virus (RSV)-infected hamster cells compared with the original transformed clones^9–11. Although several revertant RSV-hamster cells exhibited less dramatic differences in sarcoma-specific RNA, it nevertheless seemed that the transformed phenotype was directly related to the extent of transcription of the virus transforming gene sequences in this transformed/revertant cell system. A similar correlation between the amount of sarcoma-specific viral RNA and the malignant phenotype was recently reported for murine sarcoma virus-infected cells¹².