Your browser doesn't support javascript.
loading
Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin.
Ghanawi, Hanaa; Hennlein, Luisa; Zare, Abdolhossein; Bader, Jakob; Salehi, Saeede; Hornburg, Daniel; Ji, Changhe; Sivadasan, Rajeeve; Drepper, Carsten; Meissner, Felix; Mann, Matthias; Jablonka, Sibylle; Briese, Michael; Sendtner, Michael.
Afiliação
  • Ghanawi H; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg 97080, Germany.
  • Hennlein L; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg 97080, Germany.
  • Zare A; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg 97080, Germany.
  • Bader J; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried82152, Germany.
  • Salehi S; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg 97080, Germany.
  • Hornburg D; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
  • Ji C; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg 97080, Germany.
  • Sivadasan R; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg 97080, Germany.
  • Drepper C; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg 97080, Germany.
  • Meissner F; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried82152, Germany.
  • Mann M; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
  • Jablonka S; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried82152, Germany.
  • Briese M; NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
  • Sendtner M; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg 97080, Germany.
Nucleic Acids Res ; 49(21): 12284-12305, 2021 12 02.
Article em En | MEDLINE | ID: mdl-34850154
Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stress. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing giving rise to a full-length protein and a shorter isoform lacking its N-terminal acidic domain. To investigate functions selectively associated with the full-length hnRNP R isoform, we generated a Hnrnpr knockout mouse (Hnrnprtm1a/tm1a) in which expression of full-length hnRNP R was abolished while production of the truncated hnRNP R isoform was retained. Motoneurons cultured from Hnrnprtm1a/tm1a mice did not show any axonal growth defects but exhibited enhanced accumulation of double-strand breaks and an impaired DNA damage response upon exposure to genotoxic agents. Proteomic analysis of the hnRNP R interactome revealed the multifunctional protein Yb1 as a top interactor. Yb1-depleted motoneurons were defective in DNA damage repair. We show that Yb1 is recruited to chromatin upon DNA damage where it interacts with γ-H2AX, a mechanism that is dependent on full-length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its N-terminal acidic domain in this context.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Cromatina / Ribonucleoproteínas Nucleares Heterogêneas / Reparo do DNA / Proteína 1 de Ligação a Y-Box / Neurônios Motores Limite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Cromatina / Ribonucleoproteínas Nucleares Heterogêneas / Reparo do DNA / Proteína 1 de Ligação a Y-Box / Neurônios Motores Limite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2021 Tipo de documento: Article