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  Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin

Ghanawi, H., Hennlein, L., Zare, A., Bader, J., Salehi, S., Hornburg, D., et al. (2021). Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin. Nucleic Acids Research, 49(21), 12284-12305. doi:10.1093/nar/gkab1120.

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 Creators:
Ghanawi, Hanaa1, Author
Hennlein, Luisa1, Author
Zare, Abdolhossein1, Author
Bader, Jakob2, Author              
Salehi, Saeede1, Author
Hornburg, Daniel3, Author              
Ji, Changhe1, Author
Sivadasan, Rajeeve1, Author
Drepper, Carsten1, Author
Meissner, Felix3, Author              
Mann, Matthias2, Author              
Jablonka, Sibylle1, Author
Briese, Michael1, Author
Sendtner, Michael1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
3Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Free keywords: NUCLEAR RIBONUCLEOPROTEIN-R; DETERMINING GENE-PRODUCT; ACTIN MESSENGER-RNA; COMET ASSAY; GENOME-WIDE; SPINAL-CORD; YB-1; SMN; INTERACTS; ENRICHMENTBiochemistry & Molecular Biology;
 Abstract: 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 (Hnrnpr(tm1a/tm1a)) in which expression of full-length hnRNP R was abolished while production of the truncated hnRNP R isoform was retained. Motoneurons cultured from Hnrnpr(tm1a/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 gamma-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.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published in print
 Pages: 22
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000733312000024
DOI: 10.1093/nar/gkab1120
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Title: Nucleic Acids Research
  Other : Nucleic Acids Res.
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 49 (21) Sequence Number: - Start / End Page: 12284 - 12305 Identifier: ISSN: 0301-5610
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000262810