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Stress promotes RNA G-quadruplex folding in human cells

Author

Listed:
  • Prakash Kharel

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Marta Fay

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Ekaterina V. Manasova

    (Chemistry Department of Lomonosov Moscow State University)

  • Paul J. Anderson

    (Brigham and Women’s Hospital, Harvard Medical School
    Harvard Medical School Initiative for RNA Medicine)

  • Alexander V. Kurkin

    (Chemistry Department of Lomonosov Moscow State University)

  • Junjie U. Guo

    (Yale School of Medicine)

  • Pavel Ivanov

    (Brigham and Women’s Hospital, Harvard Medical School
    Harvard Medical School Initiative for RNA Medicine)

Abstract

Guanine (G)-rich nucleic acids can fold into G-quadruplex (G4) structures under permissive conditions. Although many RNAs contain sequences that fold into RNA G4s (rG4s) in vitro, their folding and functions in vivo are not well understood. In this report, we showed that the folding of putative rG4s in human cells into rG4 structures is dynamically regulated under stress. By using high-throughput dimethylsulfate (DMS) probing, we identified hundreds of endogenous stress-induced rG4s, and validated them by using an rG4 pull-down approach. Our results demonstrate that stress-induced rG4s are enriched in mRNA 3′-untranslated regions and enhance mRNA stability. Furthermore, stress-induced rG4 folding is readily reversible upon stress removal. In summary, our study revealed the dynamic regulation of rG4 folding in human cells and suggested that widespread rG4 motifs may have a global regulatory impact on mRNA stability and cellular stress response.

Suggested Citation

  • Prakash Kharel & Marta Fay & Ekaterina V. Manasova & Paul J. Anderson & Alexander V. Kurkin & Junjie U. Guo & Pavel Ivanov, 2023. "Stress promotes RNA G-quadruplex folding in human cells," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35811-x
    DOI: 10.1038/s41467-023-35811-x
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    References listed on IDEAS

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    1. Natalia Sanchez de Groot & Alexandros Armaos & Ricardo Graña-Montes & Marion Alriquet & Giulia Calloni & R. Martin Vabulas & Gian Gaetano Tartaglia, 2019. "RNA structure drives interaction with proteins," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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    Cited by:

    1. Meng Xu & Dulmi Senanayaka & Rongwei Zhao & Tafadzwa Chigumira & Astha Tripathi & Jason Tones & Rachel M. Lackner & Anne R. Wondisford & Laurel N. Moneysmith & Alexander Hirschi & Sara Craig & Sahar A, 2024. "TERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Johanna Luige & Alexandros Armaos & Gian Gaetano Tartaglia & Ulf Andersson Vang Ørom, 2024. "Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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