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Pseudouridylation of 7SK by PUS7 regulates Pol II transcription elongation

Author

Listed:
  • Yutao Zhao

    (The University of Chicago
    The University of Chicago)

  • Hui-Lung Sun

    (The University of Chicago
    The University of Chicago)

  • Wenlong Li

    (The University of Chicago
    The University of Chicago)

  • Chang Ye

    (The University of Chicago
    The University of Chicago)

  • Xiaoyang Dou

    (The University of Chicago
    The University of Chicago)

  • Yong Peng

    (The University of Chicago
    The University of Chicago)

  • Tong Wu

    (The University of Chicago
    The University of Chicago)

  • Pingluan Wang

    (The University of Chicago
    The University of Chicago)

  • Cheng-Wei Ju

    (The University of Chicago
    The University of Chicago)

  • Shun Liu

    (The University of Chicago
    The University of Chicago)

  • Yuhao Zhong

    (The University of Chicago
    The University of Chicago)

  • Qing Dai

    (The University of Chicago
    The University of Chicago)

  • Kinga Pajdzik

    (The University of Chicago
    The University of Chicago)

  • Chuan He

    (The University of Chicago
    The University of Chicago)

Abstract

Pseudouridine (Ψ) is a widespread RNA modification in various RNA species, including rRNA, tRNA, snRNA and mRNA. Ψ plays a crucial role in RNA metabolism, where it regulates pre-mRNA splicing and affects protein translation. Whether and how Ψ may regulate transcription have not been adequately studied. Here, we report that pseudouridine synthase 7 (PUS7) can mediate pseudouridylation of 7SK small nuclear RNA (snRNA), a regulator of RNA polymerase II (Pol II) promoter-proximal pausing. PUS7 loss leads to hypo-pseudouridylation of 7SK, which promotes dissociation of the positive transcription elongation factor b (P-TEFb) complex from 7SK. The release of P-TEFb from 7SK increases serine 2 phosphorylation (Ser2P) in the RNA Pol II C-terminal domain and enhances transcription elongation. In colorectal cancer (CRC) cells, the Ψ level of 7SK can be modulated by PUS7, or by site-specifically targeted pseudouridylation through dCas13b-guided system. Hypo-pseudouridylation on 7SK upon PUS7 depletion promotes KLF6/DDIT3-mediated cell apoptosis and sensitizes CRC cells to 5-FU.

Suggested Citation

  • Yutao Zhao & Hui-Lung Sun & Wenlong Li & Chang Ye & Xiaoyang Dou & Yong Peng & Tong Wu & Pingluan Wang & Cheng-Wei Ju & Shun Liu & Yuhao Zhong & Qing Dai & Kinga Pajdzik & Chuan He, 2025. "Pseudouridylation of 7SK by PUS7 regulates Pol II transcription elongation," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64668-5
    DOI: 10.1038/s41467-025-64668-5
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    References listed on IDEAS

    as
    1. Zhiyuan Yang & Qingwei Zhu & Kunxin Luo & Qiang Zhou, 2001. "The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription," Nature, Nature, vol. 414(6861), pages 317-322, November.
    2. Van Trung Nguyen & Tamás Kiss & Annemieke A. Michels & Olivier Bensaude, 2001. "7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes," Nature, Nature, vol. 414(6861), pages 322-325, November.
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