The mitogen-activated protein (MAP) kinase ERK induces tRNA synthesis by phosphorylating TFIIIB.
RNA polymerase (pol) III transcription increases within minutes of serum addition to growth-arrested fibroblasts. We show that ERK mitogen-activated protein kinases regulate pol III output by directly binding and phosphorylating the BRF1 subunit of transcription factor TFIIIB. Blocking the ERK signalling cascade inhibits TFIIIB binding to pol III and to transcription factor TFIIIC2. Chromatin immunoprecipitation shows that the association of BRF1 and pol III with tRNA(Leu) genes in cells decreases when ERK is inactivated. Furthermore, mutation of an ERK docking domain or phosphoacceptor site in BRF1 prevents serum induction of pol III transcription. These data identify a novel target for ERK, and suggest that its ability to stimulate biosynthetic capacity and growth involves direct transcriptional activation of tRNA and 5S rRNA genes.
Felton-Edkins
Zoe A
ZA
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, UK.
Fairley
Jennifer A
JA
Graham
Emma L
EL
Johnston
Imogen M
IM
White
Robert J
RJ
Scott
Pamela H
PH
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008958:Models, Molecular; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism*; D035361:Transcription Factor TFIIIB / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D021122:Protein Subunits; D035361:Transcription Factor TFIIIB; D012343:RNA, Transfer; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins