TY  - JOUR
A1  - Ghanawi, Hanaa
A1  - Hennlein, Luisa
A1  - Zare, Abdolhossein
A1  - Bader, Jakob
A1  - Salehi, Saeede
A1  - Hornburg, Daniel
A1  - Ji, Changhe
A1  - Sivadasan, Rajeeve
A1  - Drepper, Carsten
A1  - Meissner, Felix
A1  - Mann, Matthias
A1  - Jablonka, Sibylle
A1  - Briese, Michael
A1  - Sendtner, Michael
T1  - Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin
T2  - Nucleic Acids Research
N2  - 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.
KW  - nuclear ribonucleoprotein-R
KW  - determining gene-product
KW  - actin messenger RNA
KW  - comet assay
KW  - genome wide
KW  - spinal cord
KW  - YB-1
KW  - SMN
KW  - interacts
KW  - enrichment
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/26568
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-265687
VL  - 49
IS  - 21
ER  -