A role for TAF3B2 in the repression of human RNA polymerase III transcription in nonproliferating cells

RNA polymerase III (Pol III) synthesizes various small RNA species, includi ng the tRNAs and the 5 S ribosomal RNA,which are involved in protein synthe sis. Here, we describe the regulation of human Pol III transcription in res ponse to sustained cell cycle arrest. The experimental system used is a cel l line in which cell cycle arrest is induced by the regulated expression of the tumor suppressor protein p53. We show that the capacity of cells to ca rry out Pol III transcription from various promoter types, when tested in v itro, is severely reduced in response to sustained p53-mediated cell cycle arrest. Furthermore, this effect does not appear to be due to direct inhibi tion by p53. By using complementation assays, we demonstrate that a subcomp onent of the Pol III transcription factor IIIB, which contains the proteins TATA-binding protein and TAF3B2, is the target of repression. Moreover, we reveal that TAF3B2 levels are markedly reduced in extracts from cell cycle -arrested cells because of a decrease in TAF3B2 protein stability. These fi ndings provide a novel mechanism of Pol III regulation and yield insights i nto how cellular biosynthetic capacity and growth status can be coordinated .