Refine
Has Fulltext
- yes (5)
Is part of the Bibliography
- yes (5)
Document Type
- Journal article (4)
- Doctoral Thesis (1)
Language
- English (5) (remove)
Keywords
- spinal cord (2)
- Alzheimers disease (1)
- Amyotrophic-lateral-sclerosis (1)
- Axon degeneration (1)
- Axonal transport (1)
- BDNF (1)
- Ca\(_{v}\)2.2 (1)
- DAPI staining (1)
- F-actin (1)
- Intermediate filaments (1)
- Krankheit (1)
- Lacking neurofilaments (1)
- Microtubules (1)
- Missense mutation (1)
- Motoneuron (1)
- Motoneuron disease (1)
- Motoneuron diseases (1)
- Mouse model (1)
- Neurofilament (1)
- Progressive motor neuronopathy (1)
- RNA binding proteins (1)
- RNS-Bindungsproteine (1)
- SMN (1)
- Stat3 (1)
- Stathmin (1)
- Transgenic mice (1)
- YB-1 (1)
- actin messenger RNA (1)
- axons (1)
- comet assay (1)
- cytosol (1)
- determining gene-product (1)
- enrichment (1)
- genome wide (1)
- growth cone (1)
- immunoprecipitation (1)
- interacts (1)
- motor axon (1)
- nuclear ribonucleoprotein-R (1)
- protein interactions (1)
- recombinant proteins (1)
- thoracic diaphragm (1)
- trkB (1)
Institute
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.