A5058116799- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- GDF15 and Related Biomarkers
- Phagocytosis and Immune Regulation
- Nutrition and Health in Aging
- Macrophage Migration Inhibitory Factor
- Immune Response and Inflammation
- Mitochondrial Function and Pathology
- DNA and Nucleic Acid Chemistry
- Veterinary medicine and infectious diseases
- Synthesis and Biological Evaluation
- Sarcoma Diagnosis and Treatment
- HVDC Systems and Fault Protection
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
RWTH Aachen University
2012-2023
Universitätsklinikum Aachen
2009-2021
Martin Luther University Halle-Wittenberg
2004-2009
Eutropics Pharmaceuticals (United States)
2005
European Molecular Biology Laboratory
1997-2002
European Molecular Biology Laboratory
1999
Humboldt-Universität zu Berlin
1993-1994
Charité - Universitätsmedizin Berlin
1994
Although LOX mRNA accumulates early during differentiation, a differentiation control element in its 3′ untranslated region confers translational silencing until late stage erythropoiesis. We have purified two proteins from rabbit reticulocytes that specifically mediate and identified them as hnRNPs K E1. Transfection of hnRNP E1 into HeLa cells silenced the translation reporter mRNAs bearing their region. Silenced coimmunoprecipitated with K. In reconstituted cell-free system, addition...
15-lipoxygenase (LOX) expression is translationally silenced in early erythroid precursor cells by a specific mRNA-protein complex formed between the differentiation control element 3' untranslated region (UTR) and hnRNPs K E1. The 3'UTR regulatory prevents translation initiation an unknown mechanism. We demonstrate that 40S ribosomal subunit can be recruited scan to codon even when silencing bound 3'UTR. However, joining of 60S at AUG form competent 80S ribosome inhibited, unless mediated...
hnRNPK and hnRNP E1/E2 mediate translational silencing of cellular viral mRNAs in a differentiation-dependent way by binding to specific regulatory sequences. The translation 15-lipoxygenase (LOX) mRNA erythroid precursor cells the L2 human papilloma virus type 16 (HPV-16) squamous epithelial is silenced when either these immature activated maturing unknown mechanisms. Here we address question how can be translationally activated. We show that K c-Src kinase specifically interact with each...
Unraveling the molecular basis of life cycle hepatitis C virus (HCV), a prevalent agent human liver disease, entails identification cell-encoded factors that participate in replication viral RNA genome. This study provides evidence so-called NF/NFAR proteins, namely, NF90/NFAR-1, NF110/NFAR-2, NF45, and helicase A (RHA), which mostly belong to dsRBM protein family, are involved HCV process. proteins were shown specifically bind signals genomic 5′ 3′ termini promote formation looplike...
Abstract N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic mRNAs and influences many aspects of processing. miCLIP (m6A individual-nucleotide resolution UV crosslinking immunoprecipitation) an antibody-based approach to map m6A sites with single-nucleotide resolution. However, due broad antibody reactivity, reliable identification from data remains challenging. Here, we present miCLIP2 combination machine learning significantly improve detection. The...
Pathogen components, such as lipopolysaccharides of Gram-negative bacteria that activate Toll-like receptor 4, induce mitogen activated protein kinases and NFκB through different downstream pathways to stimulate pro- anti-inflammatory cytokine expression. Importantly, post-transcriptional control the expression 4 signaling molecules contributes tight regulation inflammatory synthesis in macrophages. Emerging evidence highlights role RNA-binding proteins (RBPs) innate immune response. To...
Arginine methylation is a post-translational modification found in many RNA-binding proteins. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) from HeLa cells was shown, by mass spectrometry and Edman degradation, to contain asymmetric NG,NG-dimethylarginine at five positions its amino acid sequence (Arg256, Arg258, Arg268, Arg296, Arg299). Whereas these residues were quantitatively modified, Arg303 asymmetrically dimethylated <33% of hnRNP Arg287 monomethylated <10% the protein. All...
The positive-strand RNA genome of the Hepatitis C virus (HCV) contains an internal ribosome entry site (IRES) in 5′untranslated region (5′UTR) and structured sequence elements within 3′UTR, but no poly(A) tail. Employing a limited set initiation factors, HCV IRES coordinates 5′cap-independent assembly 43S pre-initiation complex at codon located sequence. We have established Huh7 cell-derived vitro translation system that shows 3′UTR-dependent enhancement formation IRES. Through use...
Abstract Parkin is an ubiquitin‐protein ligase (E3), mutations of which cause juvenile onset – autosomal recessive Parkinson's disease, and result in reduced enzymic activity. In contrast, increased levels are protective against mitochondrial dysfunction neurodegeneration, the mechanism largely unknown. this study, 2‐DE MS proteomic techniques were utilised to investigate effects on protein expression whole cell lysates using inducible system HEK293 cells, also isolate potential interactants...
Plakophilins 1–3 (PKP1–3) are desmosomal proteins of the p120ctn family armadillo-related that essential for organizing plaque. Recent findings identified PKPs in stress granules, suggesting an association with translational machinery. However, a role controlling translation remained elusive so far. In this study, we show direct PKP1 eukaryotic initiation factor 4A1 (eIF4A1). stimulated eIF4A1-dependent via messenger RNA cap and encephalomyocarditis virus internal ribosomal entry site (IRES)...
To secure the functionality of activated macrophages in innate immune response, efficient life span control is required. Recognition bacterial lipopolysaccharides (LPS) by toll-like receptor 4 (TLR4) induces downstream signaling pathways, which merge to induce expression cytokine genes and anti-apoptotic genes. MicroRNAs (miRNAs) have emerged as important inflammatory response modulators, but information about their functional impact on apoptosis scarce. identify miRNAs differentially...
Erythroid precursor cells undergo nuclear extrusion and degradation of mitochondria when they mature to erythrocytes. It has been suggested before that the reticulocyte 15-lipoxygenase (r15-LOX) plays an important role in initiating breakdown rabbit reticulocytes. The expression r15-LOX is regulated by heterogeneous ribonucleoproteins (hnRNP) K E1 at translational level. However, this mechanism never confirmed human erythropoiesis. Based on K562 we have set up inducible erythroid cell...
Protein synthesis is a primary energy-consuming process in the cell. Therefore, under hypoxic conditions, rapid inhibition of global mRNA translation represents major protective strategy to maintain energy metabolism. How some mRNAs, especially those that encode crucial survival factors, continue be efficiently translated hypoxia not completely understood. By comparing specific transcript levels ribonucleoprotein complexes, cytoplasmic polysomes and endoplasmic reticulum (ER)-bound...
The mammalian nuclear poly(A)-binding protein, PABPN1, carries 13 asymmetrically dimethylated arginine residues in its C-terminal domain. By fractionation of cell extracts, we found that protein-arginine methyltransferases (PRMTs)-1, -3, and -6 are responsible for the modification PABPN1. Recombinant PRMT1, also methylated Our data suggest these enzymes act on their own, additional polypeptides not involved recognizing PABPN1 as a substrate. PRMT1 is predominant methyltransferase acting...
Erythroid precursor cells lose the capacity for mRNA synthesis due to exclusion of nucleus during maturation. Therefore, stability and translation mRNAs that code specific proteins, which function in late stages maturation when reticulocytes become erythrocytes, are controlled tightly. Reticulocyte 15-lipoxygenase (r15-LOX) initiates breakdown mitochondria mature reticulocytes. Through temporal restriction translation, r15-LOX is prevented premature cells. The enzyme synthesized only...
Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signaling molecules modulates the expression pro- anti-inflammatory cytokines. To address impact post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association mRNAs with heterogeneous nuclear ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating hematopoietic...