title: Direct regulation of tRNA and 5S rRNA gene transcription by Polo-like kinase 1.
abstract: Polo-like kinase Plk1 controls numerous aspects of cell-cycle progression. We show that it associates with tRNA and 5S rRNA genes and regulates their transcription by RNA polymerase III (pol III) through direct binding and phosphorylation of transcription factor Brf1. During interphase, Plk1 promotes tRNA and 5S rRNA expression by phosphorylating Brf1 directly on serine 450. However, this stimulatory modification is overridden at mitosis, when elevated Plk1 activity causes Brf1 phosphorylation on threonine 270 (T270), which prevents pol III recruitment. Thus, although Plk1 enhances net tRNA and 5S rRNA production, consistent with its proliferation-stimulating function, it also suppresses untimely transcription when cells divide. Genomic instability is apparent in cells with Brf1 T270 mutated to alanine to resist Plk1-directed inactivation, suggesting that chromosome segregation is vulnerable to inappropriate pol III activity.
authors.affiliation: Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Fairley
authors.forename: Louise E
authors.initials: LE
authors.lastname: Mitchell
authors.forename: Tracy
authors.initials: T
authors.lastname: Berg
authors.forename: Niall S
authors.initials: NS
authors.lastname: Kenneth
authors.forename: Conrad
authors.initials: C
authors.lastname: von Schubert
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Silljé
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.forename: Robert J
authors.initials: RJ
authors.lastname: White
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020090:Chromosome Segregation / Q000235:genetics; D005786:Gene Expression Regulation; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012320:RNA Polymerase III / Q000378:metabolism / Q000502:physiology; D012341:RNA, Ribosomal, 5S / Q000235:genetics*; D012343:RNA, Transfer / Q000235:genetics*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism; D035361:Transcription Factor TFIIIB / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012320:RNA Polymerase III; D012341:RNA, Ribosomal, 5S; D012343:RNA, Transfer; D035381:TATA-Binding Protein Associated Factors; D035361:Transcription Factor TFIIIB; D000097869:Polo-Like Kinase 1; C441028:BRF1 protein, human