Regulation of RNA Polymerase III Transcription by Maf1 in Mammalian Cells

Sarah J. Goodfellow; Emma L. Graham; Theodoros Kantidakis; Lynne Marshall; Beverly A. Coppins; Danuta Oficjalska-Pham; Matthieu Gérard; Olivier Lefebvre; Robert J. White

doi:10.1016/j.jmb.2008.02.060

Regulation of RNA Polymerase III Transcription by Maf1 in Mammalian Cells

Sarah J. Goodfellow
, Emma L. Graham
, Theodoros Kantidakis
, Lynne Marshall
, Beverly A. Coppins
, Danuta Oficjalska-Pham
, Matthieu Gérard
, Olivier Lefebvre
, Robert J. White^*

^*Corresponding author for this work

Aston Medical School

University of Glasgow
Division of Biochemistry and Molecular Biology
Beatson Institute for Cancer Research
CEA
Institute of Biochemistry and Biophysics of the Polish Academy of Sciences
CEA/Saclay

Research output: Contribution to journal › Article › peer-review

55 Citations (Scopus)

Abstract

RNA polymerase (pol) III produces essential components of the biosynthetic machinery; therefore, its output is tightly coupled with the rate of cell growth and proliferation. In Saccharomyces cerevisiae, Maf1 is an essential mediator of pol III repression in response to starvation. We demonstrate that a Maf1 ortholog is also used to restrain pol III activity in mouse and human cells. Mammalian Maf1 represses pol III transcription in vitro and in transfected fibroblasts. Furthermore, genetic deletion of Maf1 elevates pol III transcript expression, thus confirming the role of endogenous Maf1 as an inhibitor of mammalian pol III output. Maf1 is detected at chromosomal pol III templates in rodent and human cells. It interacts with pol III as well as its associated initiation factor TFIIIB and is phosphorylated in a serum-sensitive manner in vivo. These aspects of Maf1 function have been conserved between yeast and mammals and are therefore likely to be of fundamental importance in controlling pol III transcriptional activity.

Original language	English
Pages (from-to)	481-491
Number of pages	11
Journal	Journal of Molecular Biology
Volume	378
Issue number	3
DOIs	https://doi.org/10.1016/j.jmb.2008.02.060
Publication status	Published - 2 May 2008

Funding

This work was funded by grants 068710 and 081977 from the Wellcome Trust, grant BBS/B/0711X from the Biotechnology and Biological Sciences Research Council, grants C1288/A3143 and C1288/A4411 from Cancer Research UK (to R. J. W.) and grant 3982 from the Association pour la Recherche contre le Cancer (to O. L.). We are grateful to Arnie Berk and Yuhong Shen for providing antiserum Ab7 and VA1 plasmid, to Peter Cook for providing monoclonal antibody C39 and to Shona Murphy for providing 7SL and 7SK plasmids. We also thank Peter Geiduschek for encouraging us to use the scanning ChIP assay.

Keywords

Maf1
RNA polymerase III
TFIIIB
transcription

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10.1016/j.jmb.2008.02.060

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title = "Regulation of RNA Polymerase III Transcription by Maf1 in Mammalian Cells",

abstract = "RNA polymerase (pol) III produces essential components of the biosynthetic machinery; therefore, its output is tightly coupled with the rate of cell growth and proliferation. In Saccharomyces cerevisiae, Maf1 is an essential mediator of pol III repression in response to starvation. We demonstrate that a Maf1 ortholog is also used to restrain pol III activity in mouse and human cells. Mammalian Maf1 represses pol III transcription in vitro and in transfected fibroblasts. Furthermore, genetic deletion of Maf1 elevates pol III transcript expression, thus confirming the role of endogenous Maf1 as an inhibitor of mammalian pol III output. Maf1 is detected at chromosomal pol III templates in rodent and human cells. It interacts with pol III as well as its associated initiation factor TFIIIB and is phosphorylated in a serum-sensitive manner in vivo. These aspects of Maf1 function have been conserved between yeast and mammals and are therefore likely to be of fundamental importance in controlling pol III transcriptional activity.",

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author = "Goodfellow, \{Sarah J.\} and Graham, \{Emma L.\} and Theodoros Kantidakis and Lynne Marshall and Coppins, \{Beverly A.\} and Danuta Oficjalska-Pham and Matthieu G{\'e}rard and Olivier Lefebvre and White, \{Robert J.\}",

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doi = "10.1016/j.jmb.2008.02.060",

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T1 - Regulation of RNA Polymerase III Transcription by Maf1 in Mammalian Cells

AU - Goodfellow, Sarah J.

AU - Graham, Emma L.

AU - Kantidakis, Theodoros

AU - Marshall, Lynne

AU - Coppins, Beverly A.

AU - Oficjalska-Pham, Danuta

AU - Gérard, Matthieu

AU - Lefebvre, Olivier

AU - White, Robert J.

PY - 2008/5/2

Y1 - 2008/5/2

N2 - RNA polymerase (pol) III produces essential components of the biosynthetic machinery; therefore, its output is tightly coupled with the rate of cell growth and proliferation. In Saccharomyces cerevisiae, Maf1 is an essential mediator of pol III repression in response to starvation. We demonstrate that a Maf1 ortholog is also used to restrain pol III activity in mouse and human cells. Mammalian Maf1 represses pol III transcription in vitro and in transfected fibroblasts. Furthermore, genetic deletion of Maf1 elevates pol III transcript expression, thus confirming the role of endogenous Maf1 as an inhibitor of mammalian pol III output. Maf1 is detected at chromosomal pol III templates in rodent and human cells. It interacts with pol III as well as its associated initiation factor TFIIIB and is phosphorylated in a serum-sensitive manner in vivo. These aspects of Maf1 function have been conserved between yeast and mammals and are therefore likely to be of fundamental importance in controlling pol III transcriptional activity.

AB - RNA polymerase (pol) III produces essential components of the biosynthetic machinery; therefore, its output is tightly coupled with the rate of cell growth and proliferation. In Saccharomyces cerevisiae, Maf1 is an essential mediator of pol III repression in response to starvation. We demonstrate that a Maf1 ortholog is also used to restrain pol III activity in mouse and human cells. Mammalian Maf1 represses pol III transcription in vitro and in transfected fibroblasts. Furthermore, genetic deletion of Maf1 elevates pol III transcript expression, thus confirming the role of endogenous Maf1 as an inhibitor of mammalian pol III output. Maf1 is detected at chromosomal pol III templates in rodent and human cells. It interacts with pol III as well as its associated initiation factor TFIIIB and is phosphorylated in a serum-sensitive manner in vivo. These aspects of Maf1 function have been conserved between yeast and mammals and are therefore likely to be of fundamental importance in controlling pol III transcriptional activity.

KW - Maf1

KW - RNA polymerase III

KW - TFIIIB

KW - transcription

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ER -

Regulation of RNA Polymerase III Transcription by Maf1 in Mammalian Cells

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Keywords

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