TY  - JOUR
A1  - Van Haute, Lindsey
A1  - Dietmann, Sabine
A1  - Kremer, Laura
A1  - Hussain, Shobbir
A1  - Pearce, Sarah F.
A1  - Powell, Christopher A.
A1  - Rorbach, Joanna
A1  - Lantaff, Rebecca
A1  - Blanco, Sandra
A1  - Sauer, Sascha
A1  - Kotzaeridou, Urania
A1  - Hoffmann, Georg F.
A1  - Memari, Yasin
A1  - Kolb-Kokocinski, Anja
A1  - Durbin, Richard
A1  - Mayr, Johannes A.
A1  - Frye, Michaela
A1  - Prokisch, Holger
A1  - Minczuk, Michal
T1  - Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3
JF  - Nature Communications
N2  - Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m5C) methyltransferase NSun3 and link m5C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m5C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNAMet). Further, we demonstrate that m5C deficiency in mt-tRNAMet results in the lack of 5-formylcytosine (f5C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f5C in human mitochondrial RNA is generated by oxidative processing of m5C.
KW  - Methylation
KW  - RNA
KW  - Transferases
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165998
VL  - 7
ER  - 
TY  - JOUR
A1  - Samper Agrelo, Iria
A1  - Schira-Heinen, Jessica
A1  - Beyer, Felix
A1  - Groh, Janos
A1  - Bütermann, Christine
A1  - Estrada, Veronica
A1  - Poschmann, Gereon
A1  - Bribian, Ana
A1  - Jadasz, Janusz J.
A1  - Lopez-Mascaraque, Laura
A1  - Kremer, David
A1  - Martini, Rudolf
A1  - Müller, Hans Werner
A1  - Hartung, Hans Peter
A1  - Adjaye, James
A1  - Stühler, Kai
A1  - Küry, Patrick
T1  - Secretome analysis of mesenchymal stem cell factors fostering oligodendroglial differentiation of neural stem cells in vivo
JF  - International Journal of Molecular Sciences
N2  - Mesenchymal stem cell (MSC)-secreted factors have been shown to significantly promote oligodendrogenesis from cultured primary adult neural stem cells (aNSCs) and oligodendroglial precursor cells (OPCs). Revealing underlying mechanisms of how aNSCs can be fostered to differentiate into a specific cell lineage could provide important insights for the establishment of novel neuroregenerative treatment approaches aiming at myelin repair. However, the nature of MSC-derived differentiation and maturation factors acting on the oligodendroglial lineage has not been identified thus far. In addition to missing information on active ingredients, the degree to which MSC-dependent lineage instruction is functional in vivo also remains to be established. We here demonstrate that MSC-derived factors can indeed stimulate oligodendrogenesis and myelin sheath generation of aNSCs transplanted into different rodent central nervous system (CNS) regions, and furthermore, we provide insights into the underlying mechanism on the basis of a comparative mass spectrometry secretome analysis. We identified a number of secreted proteins known to act on oligodendroglia lineage differentiation. Among them, the tissue inhibitor of metalloproteinase type 1 (TIMP-1) was revealed to be an active component of the MSC-conditioned medium, thus validating our chosen secretome approach.
KW  - neural stem cells
KW  - mesenchymal stem cells
KW  - transplantation
KW  - oligodendroglia
KW  - glial fate modulation
KW  - myelin
KW  - spinal cord
KW  - secretome
KW  - TIMP-1
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285465
SN  - 1422-0067
VL  - 21
IS  - 12
ER  -