IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26083-4.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26083-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-26083-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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. 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.
    3. 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.
    4. Karen Adelman & Telmo Henriques, 2018. "Transcriptional speed bumps revealed in high resolution," Nature, Nature, vol. 560(7720), pages 560-561, August.
    5. 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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Kaori Asamitsu & Takatsugu Hirokawa & Takashi Okamoto, 2017. "MD simulation of the Tat/Cyclin T1/CDK9 complex revealing the hidden catalytic cavity within the CDK9 molecule upon Tat binding," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-14, February.
    2. Ryan Damme & Kongpan Li & Minjie Zhang & Jianhui Bai & Wilson H. Lee & Joseph D. Yesselman & Zhipeng Lu & Willem A. Velema, 2022. "Chemical reversible crosslinking enables measurement of RNA 3D distances and alternative conformations in cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Jennifer Porat & Moaine El Baidouri & Jorg Grigull & Jean-Marc Deragon & Mark A. Bayfield, 2022. "The methyl phosphate capping enzyme Bmc1/Bin3 is a stable component of the fission yeast telomerase holoenzyme," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Yan Li & Qianmin Wang & Yanhui Xu & Ze Li, 2024. "Structures of co-transcriptional RNA capping enzymes on paused transcription complex," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Seina Ohe & Yuji Kubota & Kiyoshi Yamaguchi & Yusuke Takagi & Junichiro Nashimoto & Hiroko Kozuka-Hata & Masaaki Oyama & Yoichi Furukawa & Mutsuhiro Takekawa, 2022. "ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. 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.
    7. Abdallah Gaballa & Anneli Gebhardt-Wolf & Bastian Krenz & Greta Mattavelli & Mara John & Giacomo Cossa & Silvia Andreani & Christina Schülein-Völk & Francisco Montesinos & Raphael Vidal & Carolin Kast, 2024. "PAF1c links S-phase progression to immune evasion and MYC function in pancreatic carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    8. Heeyoun Bunch & Deukyeong Kim & Masahiro Naganuma & Reiko Nakagawa & Anh Cong & Jaehyeon Jeong & Haruhiko Ehara & Hongha Vu & Jeong Ho Chang & Matthew J. Schellenberg & Shun-ichi Sekine, 2023. "ERK2-topoisomerase II regulatory axis is important for gene activation in immediate early genes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Jieqiong Zhang & Zhenhua Hu & Hwa Hwa Chung & Yun Tian & Kah Weng Lau & Zheng Ser & Yan Ting Lim & Radoslaw M. Sobota & Hwei Fen Leong & Benjamin Jieming Chen & Clarisse Jingyi Yeo & Shawn Ying Xuan T, 2023. "Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    10. Tatsuo Yanagisawa & Yuko Murayama & Haruhiko Ehara & Mie Goto & Mari Aoki & Shun-ichi Sekine, 2024. "Structural basis of eukaryotic transcription termination by the Rat1 exonuclease complex," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. Yujuan Liu & Jie Shu & Zhi Zhang & Ning Ding & Jinyuan Liu & Jun Liu & Yuhai Cui & Changhu Wang & Chen Chen, 2024. "A conserved Pol II elongator SPT6L mediates Pol V transcription to regulate RNA-directed DNA methylation in Arabidopsis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    12. Simona Pilotto & Michal Sýkora & Gwenny Cackett & Christopher Dulson & Finn Werner, 2024. "Structure of the recombinant RNA polymerase from African Swine Fever Virus," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    13. Ines H. Kaltheuner & Kanchan Anand & Jonas Moecking & Robert Düster & Jinhua Wang & Nathanael S. Gray & Matthias Geyer, 2021. "Abemaciclib is a potent inhibitor of DYRK1A and HIP kinases involved in transcriptional regulation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    14. Emily G. Kaye & Kavyashree Basavaraju & Geoffrey M. Nelson & Helena D. Zomer & Debarun Roy & Irene Infancy Joseph & Reza Rajabi-Toustani & Huanyu Qiao & Karen Adelman & Prabhakara P. Reddi, 2024. "RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    15. 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.
    16. Lisa-Marie Appel & Vedran Franke & Melania Bruno & Irina Grishkovskaya & Aiste Kasiliauskaite & Tanja Kaufmann & Ursula E. Schoeberl & Martin G. Puchinger & Sebastian Kostrhon & Carmen Ebenwaldner & M, 2021. "PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    17. Vladyslava Gorbovytska & Seung-Kyoon Kim & Filiz Kuybu & Michael Götze & Dahun Um & Keunsoo Kang & Andreas Pittroff & Theresia Brennecke & Lisa-Marie Schneider & Alexander Leitner & Tae-Kyung Kim & Cl, 2022. "Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    18. Shannon Ward & Alex Childs & Ceri Staley & Christopher Waugh & Julie A. Watts & Anna M. Kotowska & Rahul Bhosale & Aditi N. Borkar, 2024. "Integrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    19. Wojciech Barczak & Simon M. Carr & Geng Liu & Shonagh Munro & Annalisa Nicastri & Lian Ni Lee & Claire Hutchings & Nicola Ternette & Paul Klenerman & Alexander Kanapin & Anastasia Samsonova & Nicholas, 2023. "Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. Rina Hirano & Haruhiko Ehara & Tomoya Kujirai & Tamami Uejima & Yoshimasa Takizawa & Shun-ichi Sekine & Hitoshi Kurumizaka, 2022. "Structural basis of RNA polymerase II transcription on the chromatosome containing linker histone H1," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26083-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.