Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases.
Two cyclin-dependent kinases have been identified in yeast and mammalian RNA polymerase II transcription initiation complexes. We find that the two yeast kinases are indistinguishable in their ability to phosphorylate the RNA polymerase II CTD, and yet in living cells one kinase is a positive regulator and the other a negative regulator. This paradox is resolved by the observation that the negative regulator, Srb10, is uniquely capable of phosphorylating the CTD prior to formation of the initiation complex on promoter DNA, with consequent inhibition of transcription. In contrast, the TFIIH kinase phosphorylates the CTD only after the transcription apparatus is associated with promoter DNA. These results reveal that the timing of CTD phosphorylation can account for the positive and negative functions of the two kinases and provide a model for Srb10-dependent repression of genes involved in cell type specificity, meiosis, and sugar utilization.
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
C J
CJ
Hengartner
V E
VE
Myer
S M
SM
Liao
C J
CJ
Wilson
S S
SS
Koh
R A
RA
Young
D002453:Cell Cycle / Q000502:physiology; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism; D005656:Fungal Proteins / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D046911:Macromolecular Substances; D008540:Meiosis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012319:RNA Polymerase II / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D014158:Transcription, Genetic
D004271:DNA, Fungal; D005656:Fungal Proteins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C060137:carboxy-terminal domain kinase; D017346:Protein Serine-Threonine Kinases; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; C084210:Kin28 protein kinase, S cerevisiae; C498309:SSN3 protein, S cerevisiae; D012319:RNA Polymerase II