Journal article

Authors list: Schneider, T; Hung, LH; Aziz, M; Wilmen, A; Thaum, S; Wagner, J; Janowski, R; Müller, S; Schreiner, S; Friedhoff, P; Hüttelmaier, S; Niessing, D; Sattler, M; Schlundt, A; Bindereif, A

Publication year: 2019

Pages: 2266-

Journal: Nature Communications

Volume number: 10

ISSN: 2041-1723

Open access status: Gold

DOI Link: https://doi.org/10.1038/s41467-019-09769-8

Publisher: Nature Research

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 singledomain-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.

Harvard Citation style: Schneider, T., Hung, L., Aziz, M., Wilmen, A., Thaum, S., Wagner, J., et al. (2019) Combinatorial recognition of clustered RNA elements by the multidomain RNA-binding protein IMP3, Nature Communications, 10, p. 2266. https://doi.org/10.1038/s41467-019-09769-8

APA Citation style: Schneider, T., Hung, L., Aziz, M., Wilmen, A., Thaum, S., Wagner, J., Janowski, R., Müller, S., Schreiner, S., Friedhoff, P., Hüttelmaier, S., Niessing, D., Sattler, M., Schlundt, A., & Bindereif, A. (2019). Combinatorial recognition of clustered RNA elements by the multidomain RNA-binding protein IMP3. Nature Communications. 10, 2266. https://doi.org/10.1038/s41467-019-09769-8