A5003376279- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- interferon and immune responses
- Bone fractures and treatments
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Photodynamic Therapy Research Studies
- DNA and Nucleic Acid Chemistry
- Receptor Mechanisms and Signaling
- SARS-CoV-2 and COVID-19 Research
- Shoulder Injury and Treatment
- RNA regulation and disease
- Gastrointestinal disorders and treatments
- Crystallization and Solubility Studies
- Musculoskeletal Disorders and Rehabilitation
- Orthopaedic implants and arthroplasty
- Poxvirus research and outbreaks
- Cardiac Imaging and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Advanced MRI Techniques and Applications
- Viral Infections and Immunology Research
- Orthopedic Infections and Treatments
Rockefeller University
2015-2024
Howard Hughes Medical Institute
2013-2018
Klinikum Saarbrücken
2010-2018
New York Proton Center
2013-2015
MRC Laboratory of Molecular Biology
2015
Universität Hamburg
2011-2014
Division of Chemistry
2012
Ministry of Culture
2012
Inserm
1988-2007
Leipzig University
1998-2007
Abstract Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly recycling. Although ribosomal subunit dissociation nascent peptide are well-understood, molecular sensors mRNAs their mechanism action remain unknown. We studied Zinc Finger Protein 598 (ZNF598) using PAR-CLIP revealed that it cross-links to tRNAs, rRNAs, thereby placing protein on translating...
Highlights•Hydro-tRNAseq is a facile and efficient method for sequencing tRNAs•PAR-CLIP of SSB/La informs the annotation tRNA genes curation pre-tRNAs•Combined, they facilitate study processing POLR3 transcriptionSummaryThe participation tRNAs in fundamental aspects biology disease necessitates an accurate, experimentally confirmed sequences. This has been challenging because RNA secondary structure, nucleotide modifications, gene multiplicity complicate mapping efforts. To address these...
SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing efficacy of these drugs for treating COVID-19. Combinations both RNA-dependent polymerase and exonuclease could overcome this deficiency. Here we report identification hepatitis C virus NS5A Pibrentasvir Ombitasvir inhibitors. In presence Pibrentasvir, RNAs terminated with active forms prodrugs Sofosbuvir, Remdesivir,...
Aptamers are short nucleic acids that bind to defined targets with high affinity and specificity. The first aptamers have been selected about two decades ago by an in vitro process named SELEX (systematic evolution of ligands exponential enrichment). Since then, numerous specificities for a variety from small molecules proteins or even whole cells selected. Their applications range biosensing diagnostics therapy target-oriented drug delivery. More recently, selections using complex such as...
Reversible monoubiquitination of small subunit ribosomal proteins RPS2/uS5 and RPS3/uS3 has been noted to occur on ribosomes involved in ZNF598-dependent mRNA surveillance. Subsequent deubiquitination RPS2 RPS3 by USP10 is critical for recycling stalled a process known as ribosome-associated quality control. Here, we identify characterize the RPS2- RPS3-specific E3 ligase Really Interesting New Gene (RING) finger protein 10 (RNF10) its role translation. Overexpression RNF10 increases 40S...
This study was designed to investigate the efficacy of photodynamic therapy (PDT) in treating colonic cancer a preclinical study. Photofrin, porphyrin mixture, and pheophorbide (Ph a), bacteriochlorin, were tested on HT29 human tumor cells culture xenografted into athymic mice. Their pharmacokinetics investigated vitro, PDT at increasing concentrations determined with proliferative, cytotoxic apoptotic assessments. The vivo distribution these dyes (30 mg/kg, intraperitoneal) tumor-bearing...
Recent studies implicated the RNA-binding protein with multiple splicing (RBPMS) family of proteins in oocyte, retinal ganglion cell, heart, and gastrointestinal smooth muscle development. These contain a single RNA recognition motif (RRM), their targets molecular function have not yet been identified. We defined transcriptome-wide using photoactivatable-ribonucleoside-enhanced crosslinking immunoprecipitation (PAR-CLIP) HEK293 cells, revealing exonic mature intronic pre-mRNA binding sites,...
Aptamers represent an emerging strategy to deliver cargo molecules, including dyes, drugs, proteins or even genes, into specific target cells. Upon binding cell surface receptors aptamers can be internalized, for example by macropinocytosis receptor mediated endocytosis. Here we report the in vitro selection and characterization of RNA with high affinity (Kd = 20 nM) specificity human IL-6 (IL-6R). Importantly, these trigger uptake without compromising interaction IL-6R its natural ligands...
Abstract SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy moderate, improved treatment strategies are urgently needed. To accomplish goal, we devised strategy to identify compounds that act synergistically remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput...
Photodynamic therapy (PDT) uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on development photosensitizers specifically target cancer cells. In past few years, aptamers have been developed directly deliver cargo molecules into We conjugated photosensitizer chlorin e6 (ce6) a human interleukin-6 receptor (IL-6R) binding RNA aptamer,...
The regulation of hepatic gene expression has been extensively studied at the transcriptional level; however, control metabolism through posttranscriptional by RNA-binding proteins in physiological and disease states is less understood. Here, we report a major role for hormone-sensitive protein (RBP) APOBEC1 complementation factor (A1CF) generation hepatocyte-specific alternatively spliced transcripts. Among these transcripts are isoforms dominant high-affinity fructose-metabolizing...
Aptamers are oligonucleotides that bind targets with high specificity and affinity. They have become important tools for biosensing, target detection, drug delivery therapy. We selected the quadruplex-forming 16-mer DNA aptamer AID-1 [d(GGGT) 4] affinity interleukin-6 receptor (IL-6R) identified single nucleotide variants showed no significant loss of binding ability. The RNA counterpart [r(GGGU) also bound IL-6R as quadruplex structure. is identical to well-known HIV inhibitor T30923, which...
Interleukin-6 (IL-6) is a multifunctional cytokine that involved in the progression of various inflammatory diseases, such as rheumatoid arthritis and certain cancers; for example, multiple myeloma or hepatocellular carcinoma. To interfere with IL-6-dependent targeting IL-6 receptor (IL-6R)-presenting tumor cells using aptamers might be valuable strategy to broaden established IL-6- IL-6R-directed treatment regimens.Recently, we reported on vitro selection RNA binding human (IL-6R) nanomolar...
Aptamers are an emerging class of highly specific targeting ligands. They can be selected in vitro for a large variety targets, ranging from small molecules to whole cells. Most aptamers nucleic acid-based, allowing chemical synthesis and easy modification. Although their properties make them interesting drug candidates broad spectrum applications alternative antibodies or fusion proteins, they not yet broadly used. One major drawback is susceptibility abundant serum nucleases, resulting...
Endothelial (E-) and platelet (P-) selectin mediated adhesion of tumor cells to vascular endothelium is a pivotal step hematogenous metastasis formation. Recent studies have demonstrated that deficiency significantly reduces formation in vivo. We selected an E- P-Selectin specific DNA Aptamer (SDA) via SELEX (Systematic Evolution Ligands by EXponential enrichment) with Kd value approximately 100 nM the capability inhibiting interaction between its ligands. Employing human colorectal cancer...
Non-coding RNA biogenesis in higher eukaryotes has not been fully characterized. Here, we studied the Drosophila melanogaster Rexo5 (CG8368) protein, a metazoan-specific member of DEDDh 3'-5' single-stranded exonucleases, by genetic, biochemical, and RNA-sequencing approaches. is required for small nucleolar (snoRNA) rRNA essential D. melanogaster. Loss-of-function mutants accumulate improperly 3' end-trimmed 28S rRNA, 5S snoRNA precursors vivo. ubiquitously expressed at low levels somatic...
System-wide cross-linking and immunoprecipitation (CLIP) approaches have unveiled regulatory mechanisms of RNA-binding proteins (RBPs) mainly in cultured cells due to limitations the efficiency tissues. Here, we describe viP-CLIP (in vivo PAR-CLIP), a method capable identifying RBP targets mammalian tissues, thereby facilitating functional analysis RBP-regulatory networks vivo. We applied mouse livers identified Insig2 ApoB as prominent TIAL1 target transcripts, indicating an important role...
Trapping proteinases: The mechanism of the nonspecific human proteinase inhibitor α2-macroglobulin (α2M, about 6000 amino acid residues) is reminiscent a Venus flytrap (see scheme). structure α2M was solved recently with resolution 4.3 Å even though only one single crystal available.