P53 IS A GENERAL REPRESSOR OF RNA-POLYMERASE-III TRANSCRIPTION

p53 is a major tumour suppressor that is inactivated in a large propor tion of human cancers. We show that p53 serves as a general repressor of transcription by RNA polymerase (pol) m. It can inhibit the synthes is of a range of essential small cellular RNAs including tRNA, 5S rRNA and U6 snRNA, as well as viral products such as the adenovirus VA(I) RNA. Fibroblasts derived from p53 knock-out mice display a substantial increase in pol III transcriptional activity. Endogenous cellular p53 is shown to interact with the TATA-binding protein (TBP)-containing g eneral factor TFIIIB, thereby compromising its function severely. Howe ver, assembly of TFIIIB into a pre-initiation complex confers substant ial protection against the inhibitory effects of p53. Since TFIIIB is an essential determinant of the biosynthetic capacity of cells, its re lease from repression by p53 may contribute to a loss of growth contro l during the development of many tumours.