Regulation of RNA polymerase III transcription during hypertrophic growth.
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.
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
Sarah J
SJ
Goodfellow
Fiona
F
Innes
Louise E
LE
Derblay
W Robb
WR
MacLellan
Pamela H
PH
Scott
Robert J
RJ
White
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D049108:Cell Enlargement; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D021122:Protein Subunits / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D012341:RNA, Ribosomal, 5S / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D051381:Rats; D035361:Transcription Factor TFIIIB / Q000378:metabolism; D014158:Transcription, Genetic
D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; D012341:RNA, Ribosomal, 5S; D035361:Transcription Factor TFIIIB; D012343:RNA, Transfer; D048049:Extracellular Signal-Regulated MAP Kinases; D012320:RNA Polymerase III