TEMPORAL REGULATION OF RNA-POLYMERASE-II BY SRB10 AND KIN28 CYCLIN-DEPENDENT KINASES

Two cyclin-dependent kinases have been identified in yeast and mammali an RNA polymerase II transcription initiation complexes. We find that the two yeast kinases are indistinguishable in their ability to phosph orylate the RNA polymerase II CTD, and yet in living cells one kinase is a positive regulator and the other a negative regulator. This parad ox is resolved by the observation that the negative regulator, Srb10, is uniquely capable of phosphorylating the CTD prior to formation of t he initiation complex on promoter DNA, with consequent inhibition of t ranscription. In contrast, the TFIIH kinase phosphorylates the CTD onl y after the transcription apparatus is associated with promoter DNA. T hese results reveal that the timing of CTD phosphorylation can account for the positive and negative functions of the two kinases and provid e a model for Srb10-dependent repression of genes involved in cell typ e specificity, meiosis, and sugar utilization.