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G-quadruplex structures within the 3′ UTR of LINE-1 elements stimulate retrotransposition

Nature Structural & Molecular Biology volume 24, pages 243247 (2017) | Download Citation

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Abstract

Long interspersed nuclear elements (LINEs) are ubiquitous transposable elements in higher eukaryotes that have a significant role in shaping genomes, owing to their abundance. Here we report that guanine-rich sequences in the 3′ untranslated regions (UTRs) of hominoid-specific LINE-1 elements are coupled with retrotransposon speciation and contribute to retrotransposition through the formation of G-quadruplex (G4) structures. We demonstrate that stabilization of the G4 motif of a human-specific LINE-1 element by small-molecule ligands stimulates retrotransposition.

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Acknowledgements

S.B. is a Wellcome Trust Senior Investigator (grant 099232/z/12/z). The Balasubramanian group is supported by European Research Council Advanced Grant 339778, and receives core (C14303/A17197) and program (C9681/A18618) funding from Cancer Research UK.

Author information

Author notes

    • Aleksandr B Sahakyan
    •  & Pierre Murat

    These authors contributed equally to this work.

Affiliations

  1. Department of Chemistry, University of Cambridge, Cambridge, UK.

    • Aleksandr B Sahakyan
    • , Pierre Murat
    • , Clemens Mayer
    •  & Shankar Balasubramanian
  2. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.

    • Aleksandr B Sahakyan
    • , Pierre Murat
    • , Clemens Mayer
    •  & Shankar Balasubramanian
  3. School of Clinical Medicine, University of Cambridge, Cambridge, UK.

    • Shankar Balasubramanian

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Contributions

All authors contributed to the concepts and design of the research. A.B.S. carried out the computational analyses. P.M. and C.M. carried out the retrotransposition experiments. All authors interpreted the data. A.B.S. and P.M. wrote the manuscript with contributions from all authors. S.B. supervised the research.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Shankar Balasubramanian.

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DOI

https://doi.org/10.1038/nsmb.3367

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