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Biological Chemistry

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Volume 394, Issue 8 (Aug 2013)


Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains

Kristin Wächter
  • Institute of Molecular Medicine, Section for Molecular Cell Biology, Martin-Luther-University Halle, 06120 Halle, Germany
  • Kristin Wächter and Marcel Köhn contributed equally to this study.
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Marcel Köhn
  • Institute of Molecular Medicine, Section for Molecular Cell Biology, Martin-Luther-University Halle, 06120 Halle, Germany
  • Kristin Wächter and Marcel Köhn contributed equally to this study.
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nadine Stöhr
  • Institute of Molecular Medicine, Section for Molecular Cell Biology, Martin-Luther-University Halle, 06120 Halle, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Stefan Hüttelmaier
  • Corresponding author
  • Institute of Molecular Medicine, Section for Molecular Cell Biology, Martin-Luther-University Halle, 06120 Halle, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-05-01 | DOI: https://doi.org/10.1515/hsz-2013-0111


The IGF2 mRNA-binding protein family (IGF2BPs) directs the cytoplasmic fate of various target mRNAs and controls essential cellular functions. The three IGF2BP paralogues expressed in mammals comprise two RNA-recognition motifs (RRM) as well as four KH domains. How these domains direct IGF2BP paralogue-dependent protein function remains largely elusive. In this study, we analyze the role of KH domains in IGF2BPs by the mutational GXXG-GEEG conversion of single KH domain loops in the context of full-length polypeptides. These analyses reveal that all four KH domains of IGF2BP1 and IGF2BP2 are essentially involved in RNA-binding in vitro and the cellular association with RNA-binding proteins (RBPs). Moreover the KH domains prevent the nuclear accumulation of these two paralogues and facilitate their recruitment to stress granules. The role of KH domains appears less pronounced in IGF2BP3, because GxxG-GEEG conversion in all four KH domains only modestly affects RNA-binding, subcellular localization and RNA-dependent protein association of this paralogue. These findings indicate paralogue-dependent RNA-binding properties of IGF2BPs which likely direct distinct cellular functions. Our findings suggest that IGF2BPs contact target RNAs via all four KH domains. This implies significant structural constraints, which presumably allow the formation of exceedingly stable protein-RNA complexes.

This article offers supplementary material which is provided at the end of the article.

Keywords: cancer; CRD-BP; IGF2BP; IMP; KOC; RNA-binding protein; stress granule; VICKZ


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About the article

Corresponding author: Stefan Hüttelmaier, Institute of Molecular Medicine, Section for Molecular Cell Biology, Martin-Luther-University Halle, 06120 Halle, Germany

Received: 2013-01-14

Accepted: 2013-04-26

Published Online: 2013-05-01

Published in Print: 2013-08-01

Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2013-0111.

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©2013 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

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