A Role for TAF3B2 in the Repression of Human RNA Polymerase III Transcription in Nonproliferating Cells

Abstract

RNA polymerase III (Pol III) synthesizes various small RNA species, including the tRNAs and the 5 S ribosomal RNA, which are involved in protein synthesis. Here, we describe the regulation of human Pol III transcription in response to sustained cell cycle arrest. The experimental system used is a cell 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 carry out Pol III transcription from various promoter types, when tested in vitro, is severely reduced in response to sustained p53-mediated cell cycle arrest. Furthermore, this effect does not appear to be due to direct inhibition by p53. By using complementation assays, we demonstrate that a subcomponent 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 findings provide a novel mechanism of Pol III regulation and yield insights into how cellular biosynthetic capacity and growth status can be coordinated.

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“…2D, exogenously added CT brought up the proliferative rate of PC-3M-CTϪ cells to that of PC-3M-v2 cells (expressing carrier plasmid ptv5). Interestingly, basal proliferative activity of PC3Mv2 cells was markedly higher than R4 cells, raising a possibility that RNA polymerase III promoter, which is constitutively expressed by PC-3M-v2 cells, may induce transcription of small RNA species to nonspecifically increase the basal proliferation rate (16). This may explain why exogenously added CT could not increase the level of proliferative activity of R5 cells above that of PC-3Mv2.…”

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“…RNA polymerase III synthesizes several small RNA species, such as the tRNAs and 5 S rRNA. In cell cycle-arrested cells, BRF1 levels are markedly reduced due to a decrease in protein stability (Eichhorn and Jackson, 2001). Furthermore, pRB regulates RNA polymerase III somehow binding to BRF1 (Larminie et al, 1997).…”

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