A5091298095- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Chromatin Dynamics
- Metabolomics and Mass Spectrometry Studies
- Genetics, Bioinformatics, and Biomedical Research
- CAR-T cell therapy research
- Neurogenetic and Muscular Disorders Research
- Neurobiology and Insect Physiology Research
- CRISPR and Genetic Engineering
- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Bioinformatics and Genomic Networks
- Organ Transplantation Techniques and Outcomes
- Inflammasome and immune disorders
- Insect Utilization and Effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- 3D Surveying and Cultural Heritage
- Neuroendocrine regulation and behavior
- RNA Interference and Gene Delivery
- Liver physiology and pathology
Bristol-Myers Squibb (United States)
2025
University of Bern
2016-2023
SIB Swiss Institute of Bioinformatics
2016-2018
University of Lausanne
2016
Institut de Biologia Evolutiva
2013
Universitat Pompeu Fabra
2013
Istituto di Chimica Biomolecolare
1981
Besides degrading aberrant mRNAs that harbor a premature translation termination codon (PTC), nonsense-mediated mRNA decay (NMD) also targets many seemingly "normal" encode for full-length proteins. To identify bona fide set of such endogenous NMD in human cells, we applied meta-analysis approach which combined transcriptome profiling knockdowns and rescues the three factors UPF1, SMG6, SMG7. We provide evidence this combinatorial identifies NMD-targeted transcripts more reliably than...
Abstract Mutations in the RNA-binding protein Fused Sarcoma (FUS) cause early-onset amyotrophic lateral sclerosis (ALS). However, a detailed understanding of central RNA targets FUS and their implications for disease remain elusive. Here, we use unique blend crosslinking immunoprecipitation (CLIP) NMR spectroscopy to identify characterise physiological pathological FUS. We find that U1 snRNA is primary target via its interaction with stem-loop 3 provide atomic details this RNA-mediated mode...
Pharmacologic depletion of RNA-binding motif 39 (RBM39) using aryl sulfonamides represents a promising anti-cancer therapy but requires high levels the adaptor protein DCAF15. Consequently, novel approaches to deplete RBM39 in an DCAF15-independent manner are required. Here, we uncover that autoregulates via inclusion poison exon into its own pre-mRNA and identify cis-acting elements govern this regulation. We also determine NMR solution structures RBM39's tandem RNA recognition motifs (RRM1...
CRISPR/Cas9-based genome editing offers the possibility to knock out almost any gene of interest in an affordable and simple manner. The most common strategy is introduction a frameshift into open reading frame (ORF) target which truncates coding sequence (CDS) targets corresponding transcript for degradation by nonsense-mediated mRNA decay (NMD). However, we show that transcripts containing premature termination codons (PTCs) are not always degraded efficiently can generate C-terminally...
Accurate perception of taste information is crucial for animal survival. In adult Drosophila, gustatory receptor neurons (GRNs) perceive chemical stimuli one specific modality associated with a stereotyped behavioural response, such as aversion or attraction. We show that GRNs Drosophila larvae employ surprisingly different mode coding. Using novel method calcium imaging in the larval system, we identify multimodal GRN responds to chemicals modalities opposing valence, sweet sucrose and...
mRNA (mRNA) transport focuses the expression of encoded proteins to specific regions within cells providing them with means assume functions and even identities. BicD binding protein Egl interact microtubule motor dynein localize mRNAs in Drosophila. Because relatively few cargos were known, we isolated identified Egl::GFP associated mRNAs. The top candidates validated by qPCR, situ hybridization genetically showing that their localization requires BicD. In young embryos these target are...
The term “nonsense-mediated mRNA decay” (NMD) originally described the degradation of mRNAs with premature translation–termination codons (PTCs), but its meaning has recently been extended to be a translation-dependent post-transcriptional regulator gene expression affecting 3%–10% all mRNAs. NMD target involves both exonucleolytic and endonucleolytic pathways in mammalian cells. While latter is mediated by endonuclease SMG6, former pathway reported require complex SMG5–SMG7 or SMG5–PNRC2...
Abstract The presence of oncogenic driver mutations such as EGFR, ALK, or KRAS renders non-small cell lung adenocarcinomas sensitive to molecularly targeted therapies, however the inevitable emergence acquired drug resistance remains an unsolved clinical problem. Osimertinib, a third-generation EGFR inhibitor that was initially developed overcome EGFRT790M mutation, is now standard first-line therapy. Although various mechanisms osimertinib have been identified, specific drivers remain...
Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA pathway with roles in cellular stress responses, differentiation, and viral defense. It functions both quality control post-transcriptional regulation of gene expression. NMD has also emerged as modulator cancer progression, although available evidence supports tumor suppressor pro-tumorigenic role, depending on the model. To further investigate role cancer, we knocked out factor SMG7 HT1080 human fibrosarcoma cell line, resulting...
Relationships between evolutionary rates and gene properties on a genomic, functional, pathway, or system level are being explored to unravel the principles of process. In particular, functional network have been analyzed recognize constraints they may impose fate genes. Here we took as case study core metabolic in human erythrocytes relationship its genes flux distribution throughout it. We found that correlates with ratio nonsynonymous synonymous substitution rates. Genes encoding enzymes...
Abstract Purpose: Cereblon (CRBN), a substrate receptor of the E3 ubiquitin ligase complex CRL4CRBN, is target small molecules lenalidomide and avadomide. Upon binding drugs, Aiolos Ikaros are recruited to ligase, ubiquitylated, subsequently degraded. In diffuse large B-cell lymphoma (DLBCL) cells, direct transcriptional repressors interferon-stimulated genes (ISG) degradation these substrates results in increased ISG protein levels resulting decreased proliferation apoptosis. Herein, we...
Early data suggested that CC-115, a clinical molecule, already known to inhibit the mammalian target of rapamycin kinase (TORK) and DNA-dependent protein (DNA-PK) may have additional targets beyond TORK DNA-PK. Therefore, we aimed identify such target(s) investigate potential therapeutic applicability. Functional profiling 141 cancer cell lines revealed inhibition suppressor morphogenesis in genitalia 1 (SMG1), key regulator RNA degradation mechanism nonsense-mediated mRNA decay (NMD), as an...
ABSTRACT FUS is a multifunctional protein involved in many steps of RNA metabolism, including transcription, splicing, miRNA processing and replication-dependent histone gene expression. In this paper, we show for the first time that binds negatively regulates levels subset snoRNAs cells. Scanning available human small databases revealed existence smaller fragments can be processed from FUS-dependent snoRNAs. Therefore, suggest mediates biogenesis snoRNA-derived RNAs, called sdRNAs. Further...
Abstract Interferon‐γ (IFN‐γ) plays an important role in innate and adaptive immunity against intracellular infections is used clinically for the prevention control of chronic granulomatous disease (CGD) inborn defects IFN‐γ/interleukin (IL)‐12 axis. Using transcriptome profiling (RNA‐seq), we sought to identify differentially expressed genes, transcripts exons Epstein‐Barr virus–transformed B lymphocytes (B‐EBV) cells from CGD patients, IFN‐γ receptor deficiency normal controls, treated...
Cap binding protein 80 (Cbp80) is the larger subunit of nuclear cap-binding complex (nCBC), which known to play important roles in mRNA processing, export, stability and quality control events. Reducing Cbp80 levels female germline revealed that also involved defending against transposable elements. Combining such knockdown experiments with large scale sequencing small RNAs further showed initial biogenesis piRNAs as well secondary pathway, ping-pong amplification cycle. We found not only...
Abstract CC-99282 is a novel CELMoD® agent that was optimized for activity in non-Hodgkin lymphoma (NHL). potently degrades Ikaros and Aiolos, resulting enhanced antiproliferative, apoptotic, immune-stimulatory diffuse large B-cell (DLBCL) models, including those with acquired chemoresistance (Lopez-Girona A, et al. Hematol Oncol. 2021). In lymphocytes, negatively regulates gene expression via histone modifications, polycomb repressive complex 2 (PRC2)-mediated H3 lysine 27 trimethylation...
Abstract Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA degradation pathway that targets for faulty mRNAs with premature termination codons as well many physiological encoding full-length proteins. Consequently, NMD functions in both, quality control and post-transcriptional regulation of gene expression, it has been implicated the modulation cancer progression. To investigate role cancer, we knocked out SMG7 HT1080 human fibrosarcoma cell line. involved deadenylation-coupled...