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


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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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



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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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).

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