Direct regulation of tRNA and 5S rRNA gene transcription by Polo-like kinase 1

Jennifer A Fairley; Louise E Mitchell; Tracy Berg; Niall S Kenneth; Conrad von Schubert; Herman H W Silljé; René H Medema; Erich A Nigg; Robert J White

doi:10.1016/j.molcel.2011.11.030

Direct regulation of tRNA and 5S rRNA gene transcription by Polo-like kinase 1

Mol Cell. 2012 Feb 24;45(4):541-52. doi: 10.1016/j.molcel.2011.11.030. Epub 2012 Jan 25.

Authors

Jennifer A Fairley¹, Louise E Mitchell, Tracy Berg, Niall S Kenneth, Conrad von Schubert, Herman H W Silljé, René H Medema, Erich A Nigg, Robert J White

Affiliation

¹ Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.

PMID: 22281053
DOI: 10.1016/j.molcel.2011.11.030

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Cycle Proteins / physiology*
Chromosome Segregation / genetics
Gene Expression Regulation*
Genomic Instability
HeLa Cells
Humans
Mitosis
Mutagenesis, Site-Directed
Phosphorylation
Polo-Like Kinase 1
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
Protein Serine-Threonine Kinases / physiology*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins / physiology*
RNA Polymerase III / metabolism
RNA Polymerase III / physiology
RNA, Ribosomal, 5S / genetics*
RNA, Transfer / genetics*
TATA-Binding Protein Associated Factors / genetics
TATA-Binding Protein Associated Factors / metabolism
Transcription Factor TFIIIB / metabolism

Substances

BRF1 protein, human
Cell Cycle Proteins
Proto-Oncogene Proteins
RNA, Ribosomal, 5S
TATA-Binding Protein Associated Factors
Transcription Factor TFIIIB
RNA, Transfer
Protein Serine-Threonine Kinases
RNA Polymerase III

Grants and funding

Cancer Research UK/United Kingdom