TY  - JOUR
A1  - Veepaschit, Jyotishman
A1  - Viswanathan, Aravindan
A1  - Bordonne, Remy
A1  - Grimm, Clemens
A1  - Fischer, Utz
T1  - Identification and structural analysis of the Schizosaccharomyces pombe SMN complex
JF  - Nucleic Acids Research
N2  - The macromolecular SMN complex facilitates the formation of Sm-class ribonucleoproteins involved in mRNA processing (UsnRNPs). While biochemical studies have revealed key activities of the SMN complex, its structural investigation is lagging behind. Here we report on the identification and structural determination of the SMN complex from the lower eukaryote Schizosaccharomyces pombe, consisting of SMN, Gemin2, 6, 7, 8 and Sm proteins. The core of the SMN complex is formed by several copies of SMN tethered through its C-terminal alpha-helices arranged with alternating polarity. This creates a central platform onto which Gemin8 binds and recruits Gemins 6 and 7. The N-terminal parts of the SMN molecules extrude via flexible linkers from the core and enable binding of Gemin2 and Sm proteins. Our data identify the SMN complex as a multivalent hub where Sm proteins are collected in its periphery to allow their joining with UsnRNA.
KW  - Schizosaccharomyces pombe
KW  - SMN
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259880
VL  - 49
IS  - 13
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  -