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Regulation by the RNA-binding protein Unkempt at its effector interface

Author

Listed:
  • Kriti Shah

    (Boyce Hall
    900 University Ave)

  • Shiyang He

    (Boyce Hall
    900 University Ave)

  • David J. Turner

    (National Cancer Institute)

  • Joshua Corbo

    (National Cancer Institute
    Harvard University)

  • Khadija Rebbani

    (National Cancer Institute)

  • Daniel Dominguez

    (University of North Carolina at Chapel Hill)

  • Joseph M. Bateman

    (King’s College London)

  • Sihem Cheloufi

    (Boyce Hall
    900 University Ave
    900 University Ave)

  • Cátia Igreja

    (Max-Planck-Ring 9)

  • Eugene Valkov

    (National Cancer Institute)

  • Jernej Murn

    (Boyce Hall
    900 University Ave)

Abstract

How RNA-binding proteins (RBPs) convey regulatory instructions to the core effectors of RNA processing is unclear. Here, we document the existence and functions of a multivalent RBP–effector interface. We show that the effector interface of a conserved RBP with an essential role in metazoan development, Unkempt, is mediated by a novel type of ‘dual-purpose’ peptide motifs that can contact two different surfaces of interacting proteins. Unexpectedly, we find that the multivalent contacts do not merely serve effector recruitment but are required for the accuracy of RNA recognition by Unkempt. Systems analyses reveal that multivalent RBP–effector contacts can repurpose the principal activity of an effector for a different function, as we demonstrate for the reuse of the central eukaryotic mRNA decay factor CCR4-NOT in translational control. Our study establishes the molecular assembly and functional principles of an RBP–effector interface.

Suggested Citation

  • Kriti Shah & Shiyang He & David J. Turner & Joshua Corbo & Khadija Rebbani & Daniel Dominguez & Joseph M. Bateman & Sihem Cheloufi & Cátia Igreja & Eugene Valkov & Jernej Murn, 2024. "Regulation by the RNA-binding protein Unkempt at its effector interface," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47449-4
    DOI: 10.1038/s41467-024-47449-4
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    References listed on IDEAS

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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
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    Cited by:

    1. Sarah E. Harris & Maria S. Alexis & Gilbert Giri & Francisco F. Cavazos & Yue Hu & Jernej Murn & Maria M. Aleman & Christopher B. Burge & Daniel Dominguez, 2024. "Understanding species-specific and conserved RNA-protein interactions in vivo and in vitro," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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