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Identification of G-quadruplexes in long functional RNAs using 7-deazaguanine RNA

Nature Chemical Biology volume 13, pages 18–20 (2017)Cite this article

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Abstract

RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-substituted RNAs (FOLDeR), that allows the formation of G4s to be confirmed in long RNAs and under functional conditions.

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Figure 1: The functional Bcl-x-681 RNA contains G4s in vitro.
Figure 2: The Bcl-x-681 RNA contains G4s in functional conditions.

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Acknowledgements

This work was supported by a Medical Research Council Career Development Award (G1000526) to C.D. and a Sir Dudley Spurling Post Graduate Scholarship from the Bank of Butterfield Foundation in Bermuda to C.W. This work was also funded by CNRS and Lorraine University (UMR 7365 and previously 7214) and the European Alternative Splicing Network of Excellence (EURASNET, FP6 life sciences, genomics and biotechnology for health; LSHG-CT-2005-518238).

Author information

Authors and Affiliations

  1. Leicester Institute of Structural and Chemical Biology and Department of Molecular and Cell Biology, University of Leicester, Leicester, UK

    Carika Weldon, Ian C Eperon & Cyril Dominguez

  2. IMoPA (Ingénierie Moléculaire et Physiopathologie Articulaire), UMR 7365 Centre National de la Recherche Scientifique (CNRS)-UL, Biopôle de l'Université de Lorraine, Vandoeuvre-lès-Nancy, France

    Isabelle Behm-Ansmant & Christiane Branlant

  3. College of Pharmacy and BIO5 Institute, University of Arizona, Tucson, Arizona, USA

    Laurence H Hurley

  4. University of Arizona Cancer Center, Tucson, Arizona, USA

    Laurence H Hurley

  5. Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, UK

    Glenn A Burley

Authors
  1. Carika Weldon
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  2. Isabelle Behm-Ansmant
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  3. Laurence H Hurley
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  4. Glenn A Burley
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  5. Christiane Branlant
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  6. Ian C Eperon
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  7. Cyril Dominguez
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Contributions

C.W. performed all experiments under the guidance of I.C.E. and C.D. Footprinting experiments and structural model calculation were performed under the guidance of I.B.-A. and C.B., G.A.B. and L.H.H. contributed to the development and the validation of the strategy. C.W., I.C.E. and C.D. interpreted the results and wrote the manuscript.

Corresponding authors

Correspondence to Ian C Eperon or Cyril Dominguez.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results and Supplementary Figures 1 – 11. (PDF 13506 kb)

Supplementary Data set 1

SAFA quantification of Bcl-x-681 native footprinting. (XLSX 136 kb)

Supplementary Data set 2

Comparison of footprinting on Bcl-x-681 native and 7-deaza-G-substituted transcripts. (XLSX 122 kb)

Supplementary Data set 3

Comparison of footprinting on Bcl-x-681 in either Potassium- or lithium-containing buffers. (XLSX 131 kb)

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Weldon, C., Behm-Ansmant, I., Hurley, L. et al. Identification of G-quadruplexes in long functional RNAs using 7-deazaguanine RNA. Nat Chem Biol 13, 18–20 (2017). https://doi.org/10.1038/nchembio.2228

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  • DOI: https://doi.org/10.1038/nchembio.2228

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