Overlapping functions of the pRb family in the regulation of rRNA synthesis

The "pocket" proteins pRb, p107, and p130 are a family of negative growth r egulators. Previous studies have demonstrated that overexpression of pRb ca n repress transcription by RNA polymerase (Pol) I. To assess whether pRb pe rforms this role under physiological conditions, we have examined pre-rRNA levels in cells from mice lacking either pRb alone or combinations of the t hree pocket proteins. Pol I transcription was unaffected in pRb-knockout fi broblasts, but specific disruption of the entire pRb family deregulated rRN A synthesis. Further analysis showed that p130 shares with pRb the ability to repress Pol I transcription, whereas p107 is ineffective in this system. Production of rRNA is abnormally elevated in Rb-/- p130(-/-) fibroblasts. Furthermore, overexpression of p130 can inhibit an rRNA promoter both in vi tro and in vivo. This reflects an ability of p130 to bind and inactivate th e upstream binding factor, UBF. The data imply that rRNA synthesis in livin g cells is subject to redundant control by endogenous pRb and p130.