REPRESSION OF RNA-POLYMERASE-III TRANSCRIPTION BY THE RETINOBLASTOMA PROTEIN

TRANSCRIPTION by RNA polymerase (pol) III is under cell-cycle control, being higher in S and G2 than in G0 and early G1 phases(1-4), Many tr ansformed cell types have elevated pol III activity(4-9), presumably t o sustain sufficient protein synthesis for unrestrained growth, The re tinoblastoma tumour-suppressor protein (Rb) restricts cellular prolife ration, and is often found mutated in transformed cells(10,11). Here w e demonstrate that Rb can repress the level of transcription from pol III templates both in vitro and in vivo. Analysis of Rb-deficient SAOS 2 cells and primary fibroblasts from Rb--/- mice demonstrates elevated levels of pol III activity in the abscence of functional Rb protein, Rb-induced repression of pol III activity is alleviated by mutations i n the Rb pocket domain that occur naturally in tumours, and by viral t ransforming proteins that hind and inactivate Rb, These results implic ate repression of pol III transcription as a mechanism for Rb-induced growth arrest, and suggest that restraining protein biosynthesis may b e important in the prevention of tumour development.