Repression of RNA polymerase III transcription by the retinoblastoma protein

Abstract

Transcription by RNA polymerase (pol) III is under cell-cycle control, being higher in S and G2 than in G0 and early G1 phases. Many transformed cell types have elevated pol III activity, presumably to sustain sufficient protein synthesis for unrestrained growth. The retinoblastoma tumour-suppressor protein (Rb) restricts cellular proliferation, and is often found mutated in transformed cells. Here we demonstrate that Rb can repress the level of transcription from pol III templates both in vitro and vivo. Analysis of Rb-deficient SAOS2 cells and primary fibroblasts from Rb-/- mice demonstrates elevated levels of pol III activity in the absence of functional Rb protein. Rb-induced repression of pol III activity is alleviated by mutations in the Rb pocket domain that occur naturally in tumours, and by viral transforming proteins that bind and inactivate Rb. These results implicate repression of pol III transcription as a mechanism for Rb-induced growth arrest, and suggest that restraining protein biosynthesis may be important in the prevention of tumour development.