A5060991707- RNA modifications and cancer
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Acute Lymphoblastic Leukemia research
- Folate and B Vitamins Research
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- Pregnancy and Medication Impact
- Biochemical and Molecular Research
- IL-33, ST2, and ILC Pathways
- Clostridium difficile and Clostridium perfringens research
- Gut microbiota and health
- Antibiotic Resistance in Bacteria
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Inflammatory Bowel Disease
- RNA regulation and disease
- Bone Metabolism and Diseases
- Cancer-related gene regulation
- Lipid Membrane Structure and Behavior
- Renal Transplantation Outcomes and Treatments
- Childhood Cancer Survivors' Quality of Life
- Mesenchymal stem cell research
- Nuclear Structure and Function
- HIV Research and Treatment
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2023-2025
Max Delbrück Center
2011-2023
University of Ljubljana
2006-2023
Humboldt-Universität zu Berlin
2019
For cells to perform their biological functions, they need adopt specific shapes and form functionally distinct subcellular compartments. This is achieved in part via an asymmetric distribution of mRNAs within cells. Currently, the main model mRNA localization involves sequences called "zipcodes" that direct proper locations. However, while thousands localize cells, only a few zipcodes have been identified, suggesting additional mechanisms contribute localization. Here, we assess role...
The ribosome is an RNA-protein complex that essential for translation in all domains of life. structural and catalytic core the its ribosomal RNA (rRNA). While mutations protein (RP) genes are known drivers oncogenesis, oncogenic rRNA variants have remained elusive. We identify a cancer-specific single-nucleotide variation 18S at nucleotide 1248.U up to 45.9% patients with colorectal carcinoma (CRC) present across >22 cancer types. This site unique hyper-modified base,...
Abstract Recruitment of the human ribonucleolytic RNA exosome to nuclear polyadenylated (pA+) is facilitated by Poly(A) Tail eXosome Targeting (PAXT) connection. Besides its core dimer, formed co-factor MTR4 and ZFC3H1 protein, PAXT connection remains poorly defined. By characterizing pA+-RNA bound proteomes as well MTR4-ZFC3H1 containing complexes in conditions favoring assembly, we here uncover three additional proteins required for function: ZC3H3, RBM26 RBM27 along with known...
Single-cell transcriptional profiling reveals cell heterogeneity and clinically relevant traits in intra-operatively collected patient-derived tissue. So far, single-cell studies have been constrained by the requirement for prospectively fresh or cryopreserved This limitation might be overcome recent technical developments enabling analysis of FFPE
IL-22 plays a critical role in defending against mucosal infections, but how production is regulated incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals and single-nucleotide polymorphisms IL33 IL1RL1 associated with pneumococcal pneumonia humans. The effect of on S. was mediated by negative regulation innate lymphoid cells (ILCs) independent ILC2s as well IL-4 IL-13...
The cellular response to genotoxic stress is mediated by a well-characterized network of DNA surveillance pathways. contribution post-transcriptional gene regulatory networks the damage (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure human breast carcinoma cells ionizing radiation (IR). Interestingly, more than 260 proteins, including many nucleolar showed increased...
Introduction Alterations of the adaptive immune system have been shown to impact bone healing and may result in impaired some patients. Apart from T cells, B cells are key drivers immunity. Therefore, their role age-associated impairments might be essential understand delays during process. for formation, dysfunction has associated with aging or autoimmune diseases. But whether changes cell phenotypes involved regeneration is unknown. Methods Here, we aimed characterize early inflammatory...
Abstract The biological role of RNA-binding proteins in the secretory pathway is not well established. Here, we describe that human HDLBP/Vigilin directly interacts with more than 80% ER-localized mRNAs. PAR-CLIP analysis reveals these transcripts represent high affinity HDLBP substrates and are specifically bound their coding sequences (CDS), contrast to CDS/3’UTR-bound cytosolic crosslinks strongly long CU-rich motifs, which frequently reside CDS mRNAs result multivalent interactions. In...
Abstract Eukaryotic mRNAs are transcribed, processed, translated, and degraded in different subcellular compartments. Here, we measured mRNA flow rates between compartments mouse embryonic stem cells. By combining metabolic RNA labeling, biochemical fractionation, sequencing, mathematical modeling, determined the half-lives of nuclear pre-, mature, cytosolic, membrane-associated from over 9000 genes. In addition, estimated transcript elongation rates. Many matured have long half-lives,...
Eukaryotic mRNAs are transcribed, processed, translated, and degraded in different subcellular compartments. Here, we measured mRNA flow rates between compartments mouse embryonic stem cells. By combining metabolic RNA labeling, biochemical fractionation, sequencing, mathematical modeling, determined the half-lives of nuclear pre-, mature, cytosolic, membrane-associated from over 9000 genes. In addition, estimated transcript elongation rates. Many matured have long half-lives, indicating...
The HIV-1 Rev protein is a nuclear export factor for unspliced and incompletely spliced RNAs. Without Rev, these intron-retaining RNAs are trapped in the nucleus. A genome-wide screen identified nine proteins of spliceosome, which all enhanced expression from RNA after CRISPR/Cas knockdown. Depletion DHX38, WDR70, four Prp19-associated complex (ISY1, BUD31, XAB2, CRNKL1) resulted more than 20-fold enhancement levels cytoplasm. Targeting CRNKL1, BUD31 affected efficiencies to much larger...
The toxicity of thiopurine drugs has been correlated to the activity S-methyltransferase (TPMT), whose interindividual variation is a consequence genetic polymorphisms. We have herein investigated relevance some markers for prediction thiopurine-related toxicities and determine genotype phenotype correlation in Slovenian population. most prevalent mutant allele population TPMT*3A (4.1%), followed by TPMT*3C (0.5) TPMT*3B (0.3), while TPMT*2 was not found any examined samples. TPMT enzyme...
Although the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over recent decades, failure due to treatment-related toxicities and relapse disease still occur in about 20% patients. This retrospective study included 308 pediatric ALL patients undergoing maintenance therapy investigated effects genetic variants enzymes involved 6-mercaptopurine (6-MP) metabolism folate pathway on survival rates. The presence at least one non-functional ITPA alleles (94C>A and/or...
PAR-CLIP (photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation) facilitates the identification mapping of protein/RNA interactions. So far, it has been limited to select cell-lines as requires efficient 4SU uptake. To increase transcriptome complexity thus identify additional RNA-protein interaction sites we fused HEK 293 T-Rex cells (HEK293-Y) that express RNA binding protein YBX1 with PC12 expressing eGFP (PC12-eGFP). The resulting hybrids enable on a neuronally...