CK2-mediated stimulation of Pol I transcription by stabilization of UBF-SL1 interaction.
High levels of rRNA synthesis by RNA polymerase I are important for cell growth and proliferation. In vitro studies have indicated that the formation of a stable complex between the HMG box factor [Upstream binding factor (UBF)] and SL1 at the rRNA gene promoter is necessary to direct multiple rounds of Pol I transcription initiation. The recruitment of SL1 to the promoter occurs through protein interactions with UBF and is regulated by phosphorylation of UBF. Here we show that the protein kinase CK2 co-immunoprecipitates with the Pol I complex and is associated with the rRNA gene promoter. Inhibition of CK2 kinase activity reduces Pol I transcription in cultured cells and in vitro. Significantly, CK2 regulates the interaction between UBF and SL1 by counteracting the inhibitory effect of HMG boxes five and six through the phosphorylation of specific serines located at the C-terminus of UBF. Transcription reactions with immobilized templates indicate that phosphorylation of CK2 phosphoacceptor sites in the C-terminal domain of UBF is important for promoting multiple rounds of Pol I transcription. These data demonstrate that CK2 is recruited to the rRNA gene promoter and directly regulates Pol I transcription re-initiation by stabilizing the association between UBF and SL1.
Lin
Chih-Yin
CY
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, Los Angeles, CA 90033, USA.
Navarro
Sonia
S
Reddy
Sita
S
Comai
Lucio
L
D001665:Binding Sites; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D020459:Genes, rRNA; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012318:RNA Polymerase I / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D035463:Pol1 Transcription Initiation Complex Proteins; C428423:RRN3 protein, human; D014157:Transcription Factors; C063844:transcription factor UBF; C063660:transcription initiation factor TIF-IB; D047390:Casein Kinase II; D012318:RNA Polymerase I