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RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin

Author

Listed:
  • Roberto Bandiera

    (University of Cambridge)

  • Rebecca E. Wagner

    (German Cancer Research Center—Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280)

  • Thiago Britto-Borges

    (University Hospital Heidelberg, German Center for Cardiovascular Research (DZHK), Im Neuenheimer Feld 669)

  • Christoph Dieterich

    (University Hospital Heidelberg, German Center for Cardiovascular Research (DZHK), Im Neuenheimer Feld 669)

  • Sabine Dietmann

    (Washington University School of Medicine in St. Louis)

  • Susanne Bornelöv

    (University of Cambridge)

  • Michaela Frye

    (German Cancer Research Center—Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280)

Abstract

Pausing of RNA polymerase II (Pol II) close to promoters is a common regulatory step in RNA synthesis, and is coordinated by a ribonucleoprotein complex scaffolded by the noncoding RNA RN7SK. The function of RN7SK-regulated gene transcription in adult tissue homoeostasis is currently unknown. Here, we deplete RN7SK during mouse and human epidermal stem cell differentiation. Unexpectedly, loss of this small nuclear RNA specifically reduces transcription of numerous cell cycle regulators leading to cell cycle exit and differentiation. Mechanistically, we show that RN7SK is required for efficient transcription of highly expressed gene pairs with bidirectional promoters, which in the epidermis co-regulated cell cycle and chromosome organization. The reduction in transcription involves impaired splicing and RNA decay, but occurs in the absence of chromatin remodelling at promoters and putative enhancers. Thus, RN7SK is directly required for efficient Pol II transcription of highly transcribed bidirectional gene pairs, and thereby exerts tissue-specific functions, such as maintaining a cycling cell population in the epidermis.

Suggested Citation

  • Roberto Bandiera & Rebecca E. Wagner & Thiago Britto-Borges & Christoph Dieterich & Sabine Dietmann & Susanne Bornelöv & Michaela Frye, 2021. "RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26083-4
    DOI: 10.1038/s41467-021-26083-4
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    References listed on IDEAS

    as
    1. Karen Adelman & Telmo Henriques, 2018. "Transcriptional speed bumps revealed in high resolution," Nature, Nature, vol. 560(7720), pages 560-561, August.
    2. 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.
    3. 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.
    4. Seychelle M. Vos & Lucas Farnung & Henning Urlaub & Patrick Cramer, 2018. "Structure of paused transcription complex Pol II–DSIF–NELF," Nature, Nature, vol. 560(7720), pages 601-606, August.
    5. Seychelle M. Vos & Lucas Farnung & Marc Boehning & Christoph Wigge & Andreas Linden & Henning Urlaub & Patrick Cramer, 2018. "Structure of activated transcription complex Pol II–DSIF–PAF–SPT6," Nature, Nature, vol. 560(7720), pages 607-612, August.
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    Cited by:

    1. Sarah M. Lloyd & Daniel B. Leon & Mari O. Brady & Deborah Rodriguez & Madison P. McReynolds & Junghun Kweon & Amy E. Neely & Laura A. Blumensaadt & Patric J. Ho & Xiaomin Bao, 2022. "CDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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