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RNA G-quadruplex is resolved by repetitive and ATP-dependent mechanism of DHX36

Author

Listed:
  • Ramreddy Tippana

    (Johns Hopkins University)

  • Michael C. Chen

    (University of Cambridge
    Lung and Blood Institute)

  • Natalia A. Demeshkina

    (Lung and Blood Institute)

  • Adrian R. Ferré-D’Amaré

    (Lung and Blood Institute)

  • Sua Myong

    (Johns Hopkins University
    University of Illinois)

Abstract

DHX36 is a DEAH-box helicase that resolves parallel G-quadruplex structures formed in DNA and RNA. The recent co-crystal structure of DHX36 bound G4-DNA revealed an intimate contact, but did not address the role of ATP hydrolysis in G4 resolving activity. Here, we demonstrate that unlike on G4-DNA, DHX36 displays ATP-independent unfolding of G4-RNA followed by ATP-dependent refolding, generating a highly asymmetric pattern of activity. Interestingly, DHX36 refolds G4-RNA in several steps, reflecting the discrete steps in forming the G4 structure. We show that the ATP-dependent activity of DHX36 arises from the RNA tail rather than the G4. Mutations that perturb G4 contact result in quick dissociation of the protein from RNA upon ATP hydrolysis, while mutations that interfere with binding the RNA tail induce dysregulated activity. We propose that the ATP-dependent activity of DHX36 may be useful for dynamically resolving various G4-RNA structures in cells.

Suggested Citation

  • Ramreddy Tippana & Michael C. Chen & Natalia A. Demeshkina & Adrian R. Ferré-D’Amaré & Sua Myong, 2019. "RNA G-quadruplex is resolved by repetitive and ATP-dependent mechanism of DHX36," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09802-w
    DOI: 10.1038/s41467-019-09802-w
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    Cited by:

    1. Chun-Ying Lee & Meera Joshi & Ashley Wang & Sua Myong, 2024. "5′UTR G-quadruplex structure enhances translation in size dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Ilias Georgakopoulos-Soares & Guillermo E. Parada & Hei Yuen Wong & Ragini Medhi & Giulia Furlan & Roberto Munita & Eric A. Miska & Chun Kit Kwok & Martin Hemberg, 2022. "Alternative splicing modulation by G-quadruplexes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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