Regulation of RNA polymerase III transcription during cell cycle entry

Increased rates of RNA polymerase (pol) III transcription constitute a cent ral feature of the mitogenic response, but little is known about the mechan ism(s) responsible. We demonstrate that the retinoblastoma protein RE plays a major role in suppressing pol III transcription in growth-arrested fibro blasts. RE knockout cells are compromised in their ability to down-regulate pol III following serum withdrawal. RE binds and represses the pol III-spe cific transcription factor TFIIIB during G(0) and early G(1), but this inte raction decreases as cells approach S phase. Full induction of pol III coin cides with mid- to late G(1) phase, when RE becomes phosphorylated by cycli n D- and E-dependent kinases, TFIIIB only associates with the underphosphor ylated form of RE, and overexpression of cyclins D and E stimulates pol III transcription in vivo. The RE-related protein p130 also contributes to the repression of TFIIIB in growth-arrested fibroblasts, These observations pr ovide insight into the mechanisms responsible for controlling pol III trans cription during the switch between growth and quiescence.