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, 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.
Wellcome Trust and Cancer Research Campaign Institute of Cancer and Developmental Biology and the Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
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D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex; D012320:RNA Polymerase III / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012356:RNA, Transfer, Leu / Q000235:genetics; D012260:Ribonucleases / Q000378:metabolism; D016385:TATA Box; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C441028:BRF1 protein, human; D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D012356:RNA, Transfer, Leu; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D012320:RNA Polymerase III; D012260:Ribonucleases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex