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Nuclear export of circular RNA

Author

Listed:
  • Linh H. Ngo

    (University of Melbourne)

  • Andrew G. Bert

    (University of South Australia and SA Pathology)

  • B. Kate Dredge

    (University of South Australia and SA Pathology
    University of Adelaide
    University of Adelaide)

  • Tobias Williams

    (University of Melbourne
    Friedrich Miescher Institute for Biomedical Research)

  • Vincent Murphy

    (St Vincent’s Institute of Medical Research)

  • Wanqiu Li

    (University of Melbourne
    Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine and Institute for Biological Electron Microscopy, Southern University of Science and Technology)

  • William B. Hamilton

    (University of Melbourne)

  • Kirstyn T. Carey

    (University of Melbourne)

  • John Toubia

    (University of South Australia and SA Pathology)

  • Katherine A. Pillman

    (University of South Australia and SA Pathology
    University of Adelaide)

  • Dawei Liu

    (University of South Australia and SA Pathology)

  • Jessica Desogus

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Jeffrey A. Chao

    (Friedrich Miescher Institute for Biomedical Research)

  • Andrew J. Deans

    (St Vincent’s Institute of Medical Research)

  • Gregory J. Goodall

    (University of South Australia and SA Pathology
    University of Adelaide
    University of Adelaide)

  • Vihandha O. Wickramasinghe

    (University of Melbourne
    The University of Melbourne)

Abstract

Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells1–5, are formed by back-splicing of precursor mRNAs in the nucleus6–10. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here we identify a pathway that is specific for the nuclear export of circular RNA. This pathway requires Ran-GTP, exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter CRM1 selectively increases the nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA-binding proteins reveals that interaction between IGF2BP1 and circRNA is enhanced by Ran-GTP. The formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its interactions with exportin-2, circRNA and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Ran-GTP and exportin-2 to export circRNAs in a mechanism that is analogous to protein export, rather than mRNA export.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:nature:v:627:y:2024:i:8002:d:10.1038_s41586-024-07060-5
    DOI: 10.1038/s41586-024-07060-5
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    Cited by:

    1. 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.

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