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Transcriptome-wide identification of transient RNA G-quadruplexes in human cells

Author

Listed:
  • Sunny Y. Yang

    (University of British Columbia)

  • Pauline Lejault

    (UBFC Dijon, CNRS UMR6302)

  • Sandy Chevrier

    (Centre Georges-François Leclerc)

  • Romain Boidot

    (Centre Georges-François Leclerc)

  • A. Gordon Robertson

    (BC Cancer Agency)

  • Judy M. Y. Wong

    (University of British Columbia)

  • David Monchaud

    (UBFC Dijon, CNRS UMR6302)

Abstract

Guanine-rich RNA sequences can fold into four-stranded structures, termed G-quadruplexes (G4-RNAs), whose biological roles are poorly understood, and in vivo existence is debated. To profile biologically relevant G4-RNA in the human transcriptome, we report here on G4RP-seq, which combines G4-RNA-specific precipitation (G4RP) with sequencing. This protocol comprises a chemical crosslinking step, followed by affinity capture with the G4-specific small-molecule ligand/probe BioTASQ, and target identification by sequencing, allowing for capturing global snapshots of transiently folded G4-RNAs. We detect widespread G4-RNA targets within the transcriptome, indicative of transient G4 formation in living human cells. Using G4RP-seq, we also demonstrate that G4-stabilizing ligands (BRACO-19 and RHPS4) can change the G4 transcriptomic landscape, most notably in long non-coding RNAs. G4RP-seq thus provides a method for studying the G4-RNA landscape, as well as ways of considering the mechanisms underlying G4-RNA formation, and the activity of G4-stabilizing ligands.

Suggested Citation

  • Sunny Y. Yang & Pauline Lejault & Sandy Chevrier & Romain Boidot & A. Gordon Robertson & Judy M. Y. Wong & David Monchaud, 2018. "Transcriptome-wide identification of transient RNA G-quadruplexes in human cells," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07224-8
    DOI: 10.1038/s41467-018-07224-8
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    Cited by:

    1. 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.
    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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