TY  - JOUR
A1  - Salehi, Saeede
A1  - Zare, Abdolhossein
A1  - Prezza, Gianluca
A1  - Bader, Jakob
A1  - Schneider, Cornelius
A1  - Fischer, Utz
A1  - Meissner, Felix
A1  - Mann, Matthias
A1  - Briese, Michael
A1  - Sendtner, Michael
T1  - Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr
JF  - Nature Communications
N2  - The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol including axons and growth cones of motoneurons, and that depletion of cytosolic Ptbp2 affects axon growth. We identify Ptbp2 as a major interactor of the 3’ UTR of Hnrnpr mRNA encoding the RNA-binding protein hnRNP R. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus suggest a mechanism whereby cytosolic Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein.
KW  - molecular neuroscience
KW  - RNA-binding proteins
KW  - RNA transport
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357639
VL  - 14
ER  - 
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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265687
VL  - 49
IS  - 21
ER  -