Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling.
Synthesis of the 45S rRNA by RNA polymerase I limits cell growth. Knowledge of the mechanism of its regulation is therefore key to understanding growth control. rRNA transcription is believed to be regulated solely at initiation/promoter release. However, we found that stimulation of endogenous 45S rRNA synthesis by epidermal growth factor (EGF) and serum failed to induce an increase in RNA polymerase I engagement on the rRNA genes, despite robust enhancement of 45S rRNA synthesis. Further, endogenous transcription elongation rates were measured and found to be directly proportional to 45S rRNA synthesis. Thus, elongation is a rate-limiting step for rRNA synthesis in vivo. ERK phosphorylation of the HMG boxes of UBF, an RNA polymerase I factor essential for transcription enhancement, was shown to directly regulate elongation by inducing the remodeling of ribosomal gene chromatin. The data suggest a mechanism for coordinating the cotranscriptional assembly of preribosomal particles.
Stefanovsky
Victor
V
Cancer Research Centre and Department of Medical Biology, Laval University, Hôtel-Dieu de Québec, 11 côte du Palais, G1R 2J6 Québec, Canada.
Langlois
Frédéric
F
Gagnon-Kugler
Thérèse
T
Rothblum
Larry I
LI
Moss
Tom
T
D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004275:DNA, Ribosomal / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism* / Q000502:physiology; D012318:RNA Polymerase I / Q000096:biosynthesis / Q000235:genetics*; D012335:RNA, Ribosomal / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D004275:DNA, Ribosomal; D006133:Growth Substances; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; C088179:RNA, ribosomal, 45S; C063844:transcription factor UBF; D048049:Extracellular Signal-Regulated MAP Kinases; D012318:RNA Polymerase I