K homology domains of the mouse polycystic kidney disease-related protein, Bicaudal-C (Bicc1), mediate RNA binding in vitro

Nephron Exp Nephrol. 2008;108(1):e27-34. doi: 10.1159/000112913. Epub 2008 Jan 8.

Abstract

Background/aims: The mouse Bicc1(mBicc1) gene is the orthologue of the DrosophilaBicaudal-C(Bic-C) gene. While the role of Bicc1 in the mouse is unknown, mutations in the mouse Bicc1 gene are associated with polycystic kidney disease (PKD). The mBicc1 protein contains three K homology (KH) domains. Evidence from other KH domain-containing proteins as well as studies involving both Drosophila and Xenopus Bic-C, suggest that this motif is important in interactions with RNA.

Methods: RNA-binding assays were used to test whether mouse Bicc1 binds homoribopolymers in vitro. A series of constructs coding for different regions of the mBicc1 protein were used to determine which regions of the mBicc1 protein were important for in vitro RNA binding.

Results: Mouse Bicc1 binds homoribopolymers in vitro and the third KH domain is necessary and sufficient for in vitro RNA binding. The mutation responsible for PKD in the jcpk mouse model results in a protein that is incapable of binding RNA in vitro.

Conclusions: This study demonstrates that mouse Bicc1, a protein associated with PKD, has the ability to bind RNA in vitro. Disruption of this binding capability may be responsible for cyst formation in animals carrying mutations in the mBicc1 gene.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anopheles
  • Caenorhabditis elegans Proteins / metabolism
  • Carrier Proteins
  • Chickens
  • Drosophila melanogaster
  • Humans
  • Insect Proteins / metabolism
  • Membrane Proteins
  • Mice
  • Microtubule-Associated Proteins
  • Molecular Sequence Data
  • Pan troglodytes
  • Protein Binding / physiology
  • RNA / genetics
  • RNA / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / physiology*
  • Rats
  • Sequence Homology, Amino Acid
  • TRPP Cation Channels / metabolism*
  • Xenopus Proteins / metabolism
  • Xenopus laevis
  • Zebrafish Proteins / metabolism

Substances

  • Bicd2 protein, mouse
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Insect Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • RNA-Binding Proteins
  • TRPP Cation Channels
  • Xenopus Proteins
  • Zebrafish Proteins
  • polycystic kidney disease 1 protein
  • RNA