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

  • Kristin Wächter , Marcel Köhn , Nadine Stöhr und Stefan Hüttelmaier EMAIL logo
Veröffentlicht/Copyright: 1. Mai 2013
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 394 Heft 8

Abstract

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.

Keywords: cancer; CRD-BP; IGF2BP; IMP; KOC; RNA-binding protein; stress granule; VICKZ
Corresponding author: Stefan Hüttelmaier, Institute of Molecular Medicine, Section for Molecular Cell Biology, Martin-Luther-University Halle, 06120 Halle, Germany

The authors apologize for omitted references. This work was supported by DFG-funding (SFB610-TP/C5) to S.H. We thank Jessica L. Bell for critical reading of the manuscript.

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Received: 2013-1-14
Accepted: 2013-4-26
Published Online: 2013-05-01
Published in Print: 2013-08-01

©2013 by Walter de Gruyter Berlin Boston

Artikel in diesem Heft

  1. Masthead
  2. Masthead
  3. Guest Editorial
  4. Highlight: Protein states with cell biological and medicinal relevance
  5. HIGHLIGHT: PROTEIN STATES WITH CELL BIOLOGICAL AND MEDICAL RELEVANCE
  6. Towards improved receptor targeting: anterograde transport, internalization and postendocytic trafficking of neuropeptide Y receptors
  7. Progress in demystification of adhesion G protein-coupled receptors
  8. The unresolved puzzle why alanine extensions cause disease
  9. Molecular function of the prolyl cis/trans isomerase and metallochaperone SlyD
  10. Structure and allosteric regulation of eukaryotic 6-phosphofructokinases
  11. Polyionic and cysteine-containing fusion peptides as versatile protein tags
  12. p0071/PKP4, a multifunctional protein coordinating cell adhesion with cytoskeletal organization
  13. Lysine-specific histone demethylase LSD1 and the dynamic control of chromatin
  14. Methylation of the nuclear poly(A)-binding protein by type I protein arginine methyltransferases – how and why
  15. Oxidative in vitro folding of a cysteine deficient variant of the G protein-coupled neuropeptide Y receptor type 2 improves stability at high concentration
  16. Identification of prolyl oligopeptidase as a cyclosporine-sensitive protease by screening of mouse liver extracts
  17. In vitro maturation of Drosophila melanogaster Spätzle protein with refolded Easter reveals a novel cleavage site within the prodomain
  18. Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains
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https://doi.org/10.1515/hsz-2013-0111
Schlagwörter für diesen Artikel
cancer; CRD-BP; IGF2BP; IMP; KOC; RNA-binding protein; stress granule; VICKZ

Artikel in diesem Heft

  1. Masthead
  2. Masthead
  3. Guest Editorial
  4. Highlight: Protein states with cell biological and medicinal relevance
  5. HIGHLIGHT: PROTEIN STATES WITH CELL BIOLOGICAL AND MEDICAL RELEVANCE
  6. Towards improved receptor targeting: anterograde transport, internalization and postendocytic trafficking of neuropeptide Y receptors
  7. Progress in demystification of adhesion G protein-coupled receptors
  8. The unresolved puzzle why alanine extensions cause disease
  9. Molecular function of the prolyl cis/trans isomerase and metallochaperone SlyD
  10. Structure and allosteric regulation of eukaryotic 6-phosphofructokinases
  11. Polyionic and cysteine-containing fusion peptides as versatile protein tags
  12. p0071/PKP4, a multifunctional protein coordinating cell adhesion with cytoskeletal organization
  13. Lysine-specific histone demethylase LSD1 and the dynamic control of chromatin
  14. Methylation of the nuclear poly(A)-binding protein by type I protein arginine methyltransferases – how and why
  15. Oxidative in vitro folding of a cysteine deficient variant of the G protein-coupled neuropeptide Y receptor type 2 improves stability at high concentration
  16. Identification of prolyl oligopeptidase as a cyclosporine-sensitive protease by screening of mouse liver extracts
  17. In vitro maturation of Drosophila melanogaster Spätzle protein with refolded Easter reveals a novel cleavage site within the prodomain
  18. Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains
  19. High level expression of the Drosophila Toll receptor ectodomain and crystallization of its complex with the morphogen Spätzle
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