Gene Regulation
Cdc15 Phosphorylates the C-terminal Domain of RNA Polymerase II for Transcription during Mitosis*Cdc15 Is a Mitotic CTD Kinase

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In eukaryotes, the basal transcription in interphase is orchestrated through the regulation by kinases (Kin28, Bur1, and Ctk1) and phosphatases (Ssu72, Rtr1, and Fcp1), which act through the post-translational modification of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. The CTD comprises the repeated Tyr-Ser-Pro-Thr-Ser-Pro-Ser motif with potential epigenetic modification sites. Despite the observation of transcription and periodic expression of genes during mitosis with entailing CTD phosphorylation and dephosphorylation, the associated CTD specific kinase(s) and its role in transcription remains unknown. Here we have identified Cdc15 as a potential kinase phosphorylating Ser-2 and Ser-5 of CTD for transcription during mitosis in the budding yeast. The phosphorylation of CTD by Cdc15 is independent of any prior Ser phosphorylation(s). The inactivation of Cdc15 causes reduction of global CTD phosphorylation during mitosis and affects the expression of genes whose transcript levels peak during mitosis. Cdc15 also influences the complete transcription of clb2 gene and phosphorylates Ser-5 at the promoter and Ser-2 toward the 3′ end of the gene. The observation that Cdc15 could phosphorylate Ser-5, as well as Ser-2, during transcription in mitosis is in contrast to the phosphorylation marks put by the kinases in interphase (G1, S, and G2), where Cdck7/Kin28 phosphorylates Ser-5 at promoter and Bur1/Ctk1 phosphorylates Ser-2 at the 3′ end of the genes.

C-terminal domain (C-terminal tail domain, CTD)
chromatin
cyclin-dependent kinase 7 (CDK7)
gene regulation
mRNA
RNA polymerase II
transcription

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*

This work was supported in part by Science and Engineering Research Board (SERB) Grants EMR/2016/002167 and BSC-0118 (EpiHed) (to M. S. A.) and BSC-0103 (UNDO) (to S. K. R.) and by funds from CSIR (to A. K. S. and H. S.), University Grants Commission (UGC) (to S. R.), and Department of Biotechnology (DBT), India (to M. A.). The authors declare that they have no conflicts of interest with the contents of this article.

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The abbreviations used are:

    RNAPII

    RNA polymerase II

    CTD

    C-terminal domain

    qPCR

    quantitative PCR

    ANOVA

    analysis of variance

    CAK

    CDK-activating kinase.