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Molecular and Cellular Biology, August 2008, p. 4988-4998, Vol. 28, No. 16
0270-7306/08/$08.00+0     doi:10.1128/MCB.00492-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Phosphorylation by Casein Kinase 2 Facilitates rRNA Gene Transcription by Promoting Dissociation of TIF-IA from Elongating RNA Polymerase I {triangledown}

Holger Bierhoff,1 Miroslav Dundr,2 Annemieke A. Michels,3 and Ingrid Grummt1*

Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany,1 Rosalind Franklin University of Medicine and Science, Department of Cell Biology, North Chicago, Illinois 60064,2 Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland3

Received 26 March 2008/ Returned for modification 21 April 2008/ Accepted 5 June 2008

The protein kinase casein kinase 2 (CK2) phosphorylates different components of the RNA polymerase I (Pol I) transcription machinery and exerts a positive effect on rRNA gene (rDNA) transcription. Here we show that CK2 phosphorylates the transcription initiation factor TIF-IA at serines 170 and 172 (Ser170/172), and this phosphorylation triggers the release of TIF-IA from Pol I after transcription initiation. Inhibition of Ser170/172 phosphorylation or covalent tethering of TIF-IA to the RPA43 subunit of Pol I inhibits rDNA transcription, leading to perturbation of nucleolar structure and cell cycle arrest. Fluorescence recovery after photobleaching and chromatin immunoprecipitation experiments demonstrate that dissociation of TIF-IA from Pol I is a prerequisite for proper transcription elongation. In support of phosphorylation of TIF-IA switching from the initiation into the elongation phase, dephosphorylation of Ser170/172 by FCP1 facilitates the reassociation of TIF-IA with Pol I, allowing a new round of rDNA transcription. The results reveal a mechanism by which the functional interplay between CK2 and FCP1 sustains multiple rounds of Pol I transcription.


* Corresponding author. Mailing address: Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany. Phone: 49-6221-423423. Fax: 49-6221-423467. E-mail: I.Grummt{at}DKFZ.de

{triangledown} Published ahead of print on 16 June 2008.


Molecular and Cellular Biology, August 2008, p. 4988-4998, Vol. 28, No. 16
0270-7306/08/$08.00+0     doi:10.1128/MCB.00492-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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