A5010083961- Herpesvirus Infections and Treatments
- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Cytomegalovirus and herpesvirus research
- RNA regulation and disease
- interferon and immune responses
- Molecular Biology Techniques and Applications
- Bacteriophages and microbial interactions
- Gene expression and cancer classification
- Virus-based gene therapy research
- Breast Cancer Treatment Studies
- Plant Virus Research Studies
- Genomics and Phylogenetic Studies
- Microbial Metabolic Engineering and Bioproduction
- Cancer-related Molecular Pathways
- Toxin Mechanisms and Immunotoxins
- Viral Infections and Immunology Research
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- Animal Virus Infections Studies
- Poxvirus research and outbreaks
- Gene Regulatory Network Analysis
Ludwig-Maximilians-Universität München
2016-2025
Institute of Informatics of the Slovak Academy of Sciences
2020-2025
LMU Klinikum
2011-2023
Klinikum rechts der Isar
2006-2013
Addenbrooke's Hospital
2013
University of Duisburg-Essen
2013
University of Edinburgh
2013
Barcelona Biomedical Research Park
2013
Inform (Germany)
2013
Heidelberg University
2011
RNA levels in a cell are determined by the relative rates of synthesis and decay. State-of-the-art transcriptional analyses only employ total cellular RNA. Therefore, changes cannot be attributed to or decay, temporal resolution is poor. Recently, it was reported that newly transcribed can biosynthetically labeled for 1-2 h using thiolated nucleosides, purified from subjected microarray analysis. However, order study signaling events at molecular level, analysis occurring within minutes...
Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics available against CoVs. Knowledge host cell proteins take part pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach...
Abstract Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription RNA processing their impact on translation can be analysed single experimental setting by applying 4sU-tagging of newly transcribed ribosome profiling to lytic HSV-1 infection. Unexpectedly, find triggers the disruption termination cellular, but not viral, genes. This results extensive tens thousands nucleotides beyond...
The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading the expression of up 30 structural and non-structural protein products. functions a large number viral ORFs are poorly understood or unknown. In order gain more insight into modes action interaction different proteins, we cloned ORFeome performed genome-wide analysis for intraviral interactions intracellular localization. 900 pairwise were tested by...
RNA levels in a cell are regulated by the relative rates of synthesis and decay. We recently developed new approach for measuring both decay single experimental setting biosynthetic labeling newly transcribed RNA. Here, we show that this provides measurements half-lives from microarray data with so far unreached accuracy. Based on such human B-cells mouse fibroblasts, identified conserved regulatory principles large number biological processes. different patterns between functionally similar...
Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing variety different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 170 open reading frames. We previously reported the protein interaction networks two herpesviruses, varicella-zoster virus (VZV) Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional species, herpes simplex 1 (HSV-1), murine cytomegalovirus...
RNA synthesis and decay rates determine the steady-state levels of cellular RNAs. Metabolic tagging newly transcribed by 4-thiouridine (4sU) can reveal relative contributions rates. The kinetics processing, however, had so far remained unresolved. Here, we show that ultrashort 4sU-tagging not only provides snapshot pictures eukaryotic gene expression but, when combined with progressive RNA-seq, reveals global processing at nucleotide resolution. Using this method, identified classes rapidly...
High concentrations (> 100 µM) of the ribonucleoside analog 4-thiouridine (4sU) is widely used in methods for RNA analysis like photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) nascent messenger (m)RNA labeling (4sU-tagging). Here, we show that 4sU-tagging at low ≤ 10 µM can be to measure production processing ribosomal (r)RNA. However, elevated 4sU 50 µM), which are usually mRNA experiments, inhibit 47S rRNA. The inhibition rRNA synthesis accompanied...
BackgroundGlioblastoma (GBM), a highly malignant brain tumor, invariably recurs after therapy. Quiescent GBM cells represent potential source of tumor recurrence, but little is known about their molecular underpinnings.MethodsPatient-derived were engineered by CRISPR/Cas9-assisted knock-in an inducible histone2B-GFP (iH2B-GFP) reporter to track cell division history. We utilized in vitro 3D organoid approach isolate live quiescent (qGBM) and proliferative counterparts (pGBM) compare stem...
Abstract The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFα mRNA decay via a 3′UTR constitutive element (CDE). Here we applied PAR-CLIP to human identify ∼3,800 targets with >16,000 binding sites. A large number of sites are distinct from the consensus CDE and revealed structure-sequence motif U-rich sequences embedded in hairpins. binds preferentially short-lived DNA damage-induced mRNAs, indicating role this post-transcriptional regulation damage response. Intriguingly,...
Article25 July 2019Open Access Source DataTransparent process CDK12 controls G1/S progression by regulating RNAPII processivity at core DNA replication genes Anil Paul Chirackal Manavalan orcid.org/0000-0002-2113-0715 Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic Search for more papers this author Kveta Pilarova Michael Kluge Institut für Informatik, Ludwig-Maximilians-Universität München, Germany Koen Bartholomeeusen Michal Rajecky Jan Oppelt...
DNA damage response (DDR) involves dramatic transcriptional alterations, the mechanisms of which remain ill defined. Here, we show that following genotoxic stress, RNA-binding motif protein 7 (RBM7) stimulates RNA polymerase II (Pol II) transcription and promotes cell viability by activating positive elongation factor b (P-TEFb) via its release from inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP). This is mediated activation p38MAPK, triggers enhanced binding RBM7 with core...
Abstract The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration multi-omics data. We identify a total 201 transcripts 284 ORFs including all known 46 novel large ORFs. This includes so far unknown ORF in locus deleted FDA-approved oncolytic Imlygic. Multiple transcript isoforms...
Lytic herpes simplex virus 1 (HSV-1) infection triggers disruption of transcription termination (DoTT) most cellular genes, resulting in extensive intergenic transcription. Similarly, stress responses lead to gene-specific downstream genes (DoG). In this study, we performed a detailed comparison DoTT/DoG between HSV-1 infection, salt and heat primary human fibroblasts using 4sU-seq ATAC-seq. Although DoTT at late times was substantially more prominent than DoG stress, poly(A) read-through...
Abstract Infection by viruses, including herpes simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) RNA polymerase II (RNAPII) in host genes. However, the underlying mechanisms remain unclear. Here, we demonstrate that HSV-1 immediate early protein ICP27 induces DoTT directly binding to essential mRNA 3’ processing factor CPSF. It thereby assembly a dead-end complex, blocking cleavage. Remarkably, also acts as sequence-dependent...
The analysis of virus knockout mutants is a common approach for studying the role individual viral genes in infections and increasingly performed using functional genomics sequencing experiments, such as RNA-seq or ATAC-seq, infected cells. Identifying variants directly these experiments avoids additional genome allows confirming presence particular mutations experiment interest. Here, we present pipeline to identify from data, combining existing SNP callers with novel methods identifying...
The neurogenic loci of Drosophila are required for proper partitioning ectodermal cells into epidermal versus neural lineages. appear to encode components a developmental pathway involving cellular communication. In an effort understand the role locus mastermind in these processes, we have characterized its expression and sequence. produces number transcripts that accumulate ubiquitously during early embryogenesis but more specifically central nervous system later stages. Sequence analysis...
The development of whole-transcriptome microarrays and next-generation sequencing has revolutionized our understanding the complexity cellular gene expression. Along with a better involved molecular mechanisms, precise measurements underlying kinetics have become increasingly important. Here, these powerful methodologies face major limitations due to intrinsic properties template samples they study, i.e. total RNA. In many cases changes in RNA occur either too slowly or quickly represent...