IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-09769-8.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-09769-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-09769-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. Harald Hornegger & Aleksandra S. Anisimova & Adnan Muratovic & Benjamin Bourgeois & Elena Spinetti & Isabell Niedermoser & Roberto Covino & Tobias Madl & G. Elif Karagöz, 2024. "IGF2BP1 phosphorylation in the disordered linkers regulates ribonucleoprotein condensate formation and RNA metabolism," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    3. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09769-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.