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Selective RNA pseudouridinylation in situ by circular gRNAs in designer organelles

Author

Listed:
  • Lukas Schartel

    (Johannes Gutenberg University
    IMPRS on Cellular Biophysics)

  • Cosimo Jann

    (Johannes Gutenberg University
    Institute of Molecular Biology (IMB) Postdoc Programme)

  • Anna Wierczeiko

    (University Medical Center of the Johannes Gutenberg University)

  • Tamer Butto

    (Johannes Gutenberg-University Mainz)

  • Stefan Mündnich

    (Johannes Gutenberg-University Mainz)

  • Virginie Marchand

    (Université de Lorraine CNRS, INSERM, UAR2008/US40 IBSLor, EpiRNA-Seq Core Facility)

  • Yuri Motorin

    (Université de Lorraine CNRS, UMR7365 IMoPA)

  • Mark Helm

    (Johannes Gutenberg-University Mainz)

  • Susanne Gerber

    (University Medical Center of the Johannes Gutenberg University)

  • Edward A. Lemke

    (Johannes Gutenberg University
    Institute of Molecular Biology)

Abstract

RNA modifications play a pivotal role in the regulation of RNA chemistry within cells. Several technologies have been developed with the goal of using RNA modifications to regulate cellular biochemistry selectively, but achieving selective and precise modifications remains a challenge. Here, we show that by using designer organelles, we can modify mRNA with pseudouridine in a highly selective and guide-RNA-dependent manner. We use designer organelles inspired by concepts of phase separation, a central tenet in developing artificial membraneless organelles in living mammalian cells. In addition, we use circular guide RNAs to markedly enhance the effectiveness of targeted pseudouridinylation. Our studies introduce spatial engineering through optimized RNA editing organelles (OREO) as a complementary tool for targeted RNA modification, providing new avenues to enhance RNA modification specificity.

Suggested Citation

  • Lukas Schartel & Cosimo Jann & Anna Wierczeiko & Tamer Butto & Stefan Mündnich & Virginie Marchand & Yuri Motorin & Mark Helm & Susanne Gerber & Edward A. Lemke, 2024. "Selective RNA pseudouridinylation in situ by circular gRNAs in designer organelles," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53403-1
    DOI: 10.1038/s41467-024-53403-1
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    References listed on IDEAS

    as
    1. John Karijolich & Yi-Tao Yu, 2011. "Converting nonsense codons into sense codons by targeted pseudouridylation," Nature, Nature, vol. 474(7351), pages 395-398, June.
    2. Linh H. Ngo & Andrew G. Bert & B. Kate Dredge & Tobias Williams & Vincent Murphy & Wanqiu Li & William B. Hamilton & Kirstyn T. Carey & John Toubia & Katherine A. Pillman & Dawei Liu & Jessica Desogus, 2024. "Publisher Correction: Nuclear export of circular RNA," Nature, Nature, vol. 627(8005), pages 12-12, March.
    3. Linh H. Ngo & Andrew G. Bert & B. Kate Dredge & Tobias Williams & Vincent Murphy & Wanqiu Li & William B. Hamilton & Kirstyn T. Carey & John Toubia & Katherine A. Pillman & Dawei Liu & Jessica Desogus, 2024. "Nuclear export of circular RNA," Nature, Nature, vol. 627(8002), pages 212-220, March.
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