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Combinatorial recognition of clustered RNA elements by the multidomain RNA-binding protein IMP3

Author

Listed:
  • Tim Schneider

    (Justus-Liebig-University of Giessen)

  • Lee-Hsueh Hung

    (Justus-Liebig-University of Giessen)

  • Masood Aziz

    (Technical University of Munich (TUM)
    Helmholtz-Zentrum München)

  • Anna Wilmen

    (Justus-Liebig-University of Giessen)

  • Stephanie Thaum

    (Justus-Liebig-University of Giessen)

  • Jacqueline Wagner

    (Technical University of Munich (TUM))

  • Robert Janowski

    (Helmholtz-Zentrum München)

  • Simon Müller

    (Martin Luther University Halle-Wittenberg)

  • Silke Schreiner

    (Justus-Liebig-University of Giessen)

  • Peter Friedhoff

    (Justus-Liebig-University of Giessen)

  • Stefan Hüttelmaier

    (Martin Luther University Halle-Wittenberg)

  • Dierk Niessing

    (Helmholtz-Zentrum München
    Ulm University)

  • Michael Sattler

    (Technical University of Munich (TUM)
    Helmholtz-Zentrum München)

  • Andreas Schlundt

    (Technical University of Munich (TUM)
    Helmholtz-Zentrum München
    Goethe-University Frankfurt)

  • Albrecht Bindereif

    (Justus-Liebig-University of Giessen)

Abstract

How multidomain RNA-binding proteins recognize their specific target sequences, based on a combinatorial code, represents a fundamental unsolved question and has not been studied systematically so far. Here we focus on a prototypical multidomain RNA-binding protein, IMP3 (also called IGF2BP3), which contains six RNA-binding domains (RBDs): four KH and two RRM domains. We establish an integrative systematic strategy, combining single-domain-resolved SELEX-seq, motif-spacing analyses, in vivo iCLIP, functional validation assays, and structural biology. This approach identifies the RNA-binding specificity and RNP topology of IMP3, involving all six RBDs and a cluster of up to five distinct and appropriately spaced CA-rich and GGC-core RNA elements, covering a >100 nucleotide-long target RNA region. Our generally applicable approach explains both specificity and flexibility of IMP3-RNA recognition, allows the prediction of IMP3 targets, and provides a paradigm for the function of multivalent interactions with multidomain RNA-binding proteins in gene regulation.

Suggested Citation

  • Tim Schneider & Lee-Hsueh Hung & Masood Aziz & Anna Wilmen & Stephanie Thaum & Jacqueline Wagner & Robert Janowski & Simon Müller & Silke Schreiner & Peter Friedhoff & Stefan Hüttelmaier & Dierk Niess, 2019. "Combinatorial recognition of clustered RNA elements by the multidomain RNA-binding protein IMP3," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09769-8
    DOI: 10.1038/s41467-019-09769-8
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    Cited by:

    1. Komal Soni & Pravin Kumar Ankush Jagtap & Santiago Martínez-Lumbreras & Sophie Bonnal & Arie Geerlof & Ralf Stehle & Bernd Simon & Juan Valcárcel & Michael Sattler, 2023. "Structural basis for specific RNA recognition by the alternative splicing factor RBM5," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Chang Liu & Xiaoyang Dou & Yutao Zhao & Linda Zhang & Lisheng Zhang & Qing Dai & Jun Liu & Tong Wu & Yu Xiao & Chuan He, 2024. "IGF2BP3 promotes mRNA degradation through internal m7G modification," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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