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Nat Commun. 2018 Feb 7;9(1):543. doi: 10.1038/s41467-018-03006-4.

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

Author information

1
Department of Molecular Biology and Genetics, Cornell University, 107 Biotechnology Building, 526 Campus Road, Ithaca, NY, 14853-2703, USA.
2
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
3
Department of Molecular Biology and Genetics, Cornell University, 107 Biotechnology Building, 526 Campus Road, Ithaca, NY, 14853-2703, USA. johnlis@cornell.edu.

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.

PMID:
29416031
PMCID:
PMC5803247
DOI:
10.1038/s41467-018-03006-4
[Indexed for MEDLINE]
Free PMC Article

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