Yujin Inayoshi

Publications (2)9.55 Total impact

• Source

  Available from: Rudolf Volkmer

  Article: Y65C missense mutation in the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1 affects its binding activity and deregulates pre-mRNA splicing.

  Victor E Tapia, Emilia Nicolaescu, Caleb B McDonald, Valeria Musi, Tsutomu Oka, Yujin Inayoshi, Adam C Satteson, Virginia Mazack, Jasper Humbert, Christian J Gaffney, Monique Beullens, Charles E Schwartz, Christiane Landgraf, Rudolf Volkmer, Annalisa Pastore, Amjad Farooq, Mathieu Bollen, Marius Sudol
  [show abstract] [hide abstract]
  ABSTRACT: The PQBP1 (polyglutamine tract-binding protein 1) gene encodes a nuclear protein that regulates pre-mRNA splicing and transcription. Mutations in the PQBP1 gene were reported in several X chromosome-linked mental retardation disorders including Golabi-Ito-Hall syndrome. The missense mutation that causes this syndrome is unique among other PQBP1 mutations reported to date because it maps within a functional domain of PQBP1, known as the WW domain. The mutation substitutes tyrosine 65 with cysteine and is located within the conserved core of aromatic amino acids of the domain. We show here that the binding property of the Y65C-mutated WW domain and the full-length mutant protein toward its cognate proline-rich ligands was diminished. Furthermore, in Golabi-Ito-Hall-derived lymphoblasts we showed that the complex between PQBP1-Y65C and WBP11 (WW domain-binding protein 11) splicing factor was compromised. In these cells a substantial decrease in pre-mRNA splicing efficiency was detected. Our study points to the critical role of the WW domain in the function of the PQBP1 protein and provides an insight into the molecular mechanism that underlies the X chromosome-linked mental retardation entities classified globally as Renpenning syndrome.
  Journal of Biological Chemistry 06/2010; 285(25):19391-401. · 4.77 Impact Factor
• Article: Y65C Missense Mutation in the WW Domain of the Golabi-Ito-Hall Syndrome Protein PQBP1 Affects Its Binding Activity and Deregulates Pre-mRNA Splicing

  Victor E. Tapia, Emilia Nicolaescu, Caleb B. McDonald, Valeria Musi, Tsutomu Oka, Yujin Inayoshi, Adam C. Satteson, Virginia Mazack, Jasper Humbert, Christian J. Gaffney, Monique Beullens, Charles E. Schwartz, Christiane Landgraf, Rudolf Volkmer, Annalisa Pastore, Amjad Farooq, Mathieu Bollen, Marius Sudol
  [show abstract] [hide abstract]
  ABSTRACT: The PQBP1 (polyglutamine tract-binding protein 1) gene encodes a nuclear protein that regulates pre-mRNA splicing and transcription. Mutations in the PQBP1 gene were reported in several X chromosome-linked mental retardation disorders including Golabi-Ito-Hall syndrome. The missense mutation that causes this syndrome is unique among other PQBP1 mutations reported to date because it maps within a functional domain of PQBP1, known as the WW domain. The mutation substitutes tyrosine 65 with cysteine and is located within the conserved core of aromatic amino acids of the domain. We show here that the binding property of the Y65C-mutated WW domain and the full-length mutant protein toward its cognate proline-rich ligands was diminished. Furthermore, in Golabi-Ito-Hall-derived lymphoblasts we showed that the complex between PQBP1-Y65C and WBP11 (WW domain-binding protein 11) splicing factor was compromised. In these cells a substantial decrease in pre-mRNA splicing efficiency was detected. Our study points to the critical role of the WW domain in the function of the PQBP1 protein and provides an insight into the molecular mechanism that underlies the X chromosome-linked mental retardation entities classified globally as Renpenning syndrome.
  Journal of Biological Chemistry 06/2010; 285(25):19391-19401. · 4.77 Impact Factor