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Cdk9 regulates a promoter-proximal checkpoint to modulate RNA polymerase II elongation rate in fission yeast

Author

Listed:
  • Gregory T. Booth

    (Cornell University)

  • Pabitra K. Parua

    (Icahn School of Medicine at Mount Sinai)

  • Miriam Sansó

    (Icahn School of Medicine at Mount Sinai)

  • Robert P. Fisher

    (Icahn School of Medicine at Mount Sinai)

  • John T. Lis

    (Cornell University)

Abstract

Post-translational modifications of the transcription elongation complex provide mechanisms to fine-tune gene expression, yet their specific impacts on RNA polymerase II regulation remain difficult to ascertain. Here, in Schizosaccharomyces pombe, we examine the role of Cdk9, and related Mcs6/Cdk7 and Lsk1/Cdk12 kinases, on transcription at base-pair resolution with Precision Run-On sequencing (PRO-seq). Within a minute of Cdk9 inhibition, phosphorylation of Pol II-associated factor, Spt5 is undetectable. The effects of Cdk9 inhibition are more severe than inhibition of Cdk7 and Cdk12, resulting in a shift of Pol II toward the transcription start site (TSS). A time course of Cdk9 inhibition reveals that early transcribing Pol II can escape promoter-proximal regions, but with a severely reduced elongation rate of only ~400 bp/min. Our results in fission yeast suggest the existence of a conserved global regulatory checkpoint that requires Cdk9 kinase activity.

Suggested Citation

  • Gregory T. Booth & Pabitra K. Parua & Miriam Sansó & Robert P. Fisher & John T. Lis, 2018. "Cdk9 regulates a promoter-proximal checkpoint to modulate RNA polymerase II elongation rate in fission yeast," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03006-4
    DOI: 10.1038/s41467-018-03006-4
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    Cited by:

    1. Michael DeBerardine & Gregory T. Booth & Philip P. Versluis & John T. Lis, 2023. "The NELF pausing checkpoint mediates the functional divergence of Cdk9," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Anniina Vihervaara & Philip Versluis & Samu V. Himanen & John T. Lis, 2023. "PRO-IP-seq tracks molecular modifications of engaged Pol II complexes at nucleotide resolution," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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