Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes

Abstract

G-quadruplexes (G4) are extremely stable secondary structures forming stacks of guanine tetrads. DNA G4 structures have been extensively studied, however, less is known about G4 motifs in mRNAs, especially in their coding sequences. Herein, we show that Aven stimulates the mRNA translation of the mixed lineage leukemia (MLL) proto-oncogene in an arginine methylation-dependent manner. The Aven RGG/RG motif bound G4 structures within the coding regions of the MLL1 and MLL4 mRNAs increasing their polysomal association and translation, resulting in the induction of transcription of leukemic genes. The DHX36 RNA helicase associated with the Aven complex and was required for optimal translation of G4 mRNAs. Depletion of Aven led to a decrease in synthesis of MLL1 and MLL4 proteins esulting in reduced proliferation of leukemic cells. These findings identify an Aven-centered complex that stimulates the translation of G4 harboring mRNAs, thereby promoting survival of leukemic cells.

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Author details

  1. Palaniraja Thandapani

    Terry Fox Molecular Oncology Group, Segal Cancer Center, Jewish General Hospital, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Jingwen Song

    Terry Fox Molecular Oncology Group, Segal Cancer Center, Jewish General Hospital, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Valentina Gandin

    Terry Fox Molecular Oncology Group, Segal Cancer Center, Jewish General Hospital, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Yutian Cai

    Terry Fox Molecular Oncology Group, Segal Cancer Center, Jewish General Hospital, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Samuel G Rouleau

    Département de Biochimie, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Jean-Michel Garant

    Département de Biochimie, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Francois-Michel Boisvert

    Département d'Anatomie et de Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Pavillon de Recherche Appliquée au Cancer, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Zhenbao Yu

    Terry Fox Molecular Oncology Group, Segal Cancer Center, Jewish General Hospital, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Jean-Pierre Perreault

    Département de Biochimie, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Ivan Topisirovic

    Terry Fox Molecular Oncology Group, Segal Cancer Center, Jewish General Hospital, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  11. Stéphane Richard

    Terry Fox Molecular Oncology Group, Segal Cancer Center, McGill University, Montreal, Canada
    For correspondence
    stephane.richard@mcgill.ca
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Thandapani et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Palaniraja Thandapani
  2. Jingwen Song
  3. Valentina Gandin
  4. Yutian Cai
  5. Samuel G Rouleau
  6. Jean-Michel Garant
  7. Francois-Michel Boisvert
  8. Zhenbao Yu
  9. Jean-Pierre Perreault
  10. Ivan Topisirovic
  11. Stéphane Richard
(2015)
Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes
eLife 4:e06234.
https://doi.org/10.7554/eLife.06234

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https://doi.org/10.7554/eLife.06234

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