IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58479-x.html
   My bibliography  Save this article

DNA supercoiling-mediated G4/R-loop formation tunes transcription by controlling the access of RNA polymerase

Author

Listed:
  • Jihee Hwang

    (Boston Children’s Hospital and Harvard Medical School)

  • Chun-Ying Lee

    (Boston Children’s Hospital and Harvard Medical School)

  • Sumitabha Brahmachari

    (Rice University)

  • Shubham Tripathi

    (Yale School of Medicine)

  • Tapas Paul

    (Boston Children’s Hospital and Harvard Medical School)

  • Huijin Lee

    (Johns Hopkins University School of Medicine)

  • Alanna Craig

    (Johns Hopkins University)

  • Taekjip Ha

    (Boston Children’s Hospital and Harvard Medical School
    Johns Hopkins University School of Medicine
    Johns Hopkins University
    Johns Hopkins University)

  • Sua Myong

    (Boston Children’s Hospital and Harvard Medical School
    Johns Hopkins University School of Medicine
    Johns Hopkins University)

Abstract

RNA polymerase (RNAP) is a processive motor that modulates DNA supercoiling and reshapes DNA structures. The feedback loop between the DNA topology and transcription remains elusive. Here, we investigate the impact of potential G-quadruplex forming sequences (PQS) on transcription in response to DNA supercoiling. We find that supercoiled DNA increases transcription frequency 10-fold higher than relaxed DNA, which lead to an abrupt formation of G-quadruplex (G4) and R-loop structures. Moreover, the stable R-loop relieves topological strain, facilitated by G4 formation. The cooperative formation of G4/R-loop effectively alters the DNA topology around the promoter and suppresses transcriptional activity by impeding RNAP loading. These findings highlight negative supercoiling as a built-in spring that triggers a transcriptional burst followed by a rapid suppression upon G4/R-loop formation. This study sheds light on the intricate interplay between DNA topology and structural change in transcriptional regulation, with implications for understanding gene expression dynamics.

Suggested Citation

  • Jihee Hwang & Chun-Ying Lee & Sumitabha Brahmachari & Shubham Tripathi & Tapas Paul & Huijin Lee & Alanna Craig & Taekjip Ha & Sua Myong, 2025. "DNA supercoiling-mediated G4/R-loop formation tunes transcription by controlling the access of RNA polymerase," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58479-x
    DOI: 10.1038/s41467-025-58479-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58479-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58479-x?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
    ---><---

    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:16:y:2025:i:1:d:10.1038_s41467-025-58479-x. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.