Article
- The EMBO Journal (2006) 25, 1522 - 1533
- doi:10.1038/sj.emboj.7601040
Published online: 16 March 2006
Subject Categories:
Regulation of RNA polymerase III transcription during hypertrophic growth
Sarah J Goodfellow1, Fiona Innes1, Louise E Derblay1, W Robb MacLellan2, Pamela H Scott1 and Robert J White1,3
- Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK
- Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Beatson Institute for Cancer Research, Bearsden, Glasgow, UK
Correspondence to:
Robert J White, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. Tel.: +44 141 330 3953; Fax: +44 141 942 6521; E-mail: r.white@beatson.gla.ac.uk
Received 17 October 2005; Accepted 20 February 2006
Abstract
The cell division-independent growth of terminally differentiated cardiomyocytes is commonly associated with cardiovascular disease. We demonstrate that it is accompanied by a substantial rise in transcription by RNA polymerase (pol) III, which produces essential components of the biosynthetic apparatus, including 5S rRNA and tRNAs. This increase in transcription is achieved by changes in both the activity and level of the essential pol III-specific transcription factor TFIIIB. Erk and c-Myc, which directly activate TFIIIB in proliferating fibroblasts, also induce pol III transcription in growing cardiomyocytes. Furthermore, hypertrophic stimulation increases expression of the essential TFIIIB subunit Brf1, an effect not seen when fibroblasts proliferate. Erk mediates this induction of Brf1 expression and therefore contributes in at least two ways to pol III transcriptional activation during hypertrophy. Increased production of tRNA and 5S rRNA will contribute to the enhanced translational capacity required to sustain hypertrophic growth.
Keywords:
- c-Myc,
- Erk,
- hypertrophy,
- pol III transcription,
- TFIIIB
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