- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Advanced Electron Microscopy Techniques and Applications
- HIV Research and Treatment
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Viral Infections and Vectors
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- HIV/AIDS drug development and treatment
- thermodynamics and calorimetric analyses
- Ubiquitin and proteasome pathways
- nanoparticles nucleation surface interactions
- RNA Research and Splicing
Max Delbrück Center
2024
Charité - Universitätsmedizin Berlin
2017-2021
Freie Universität Berlin
2021
Humboldt-Universität zu Berlin
2021
Institut de génétique et de biologie moléculaire et cellulaire
2016
Inserm
2016
Abstract Eukaryotic RNA polymerase I (Pol I) is specialized in rRNA gene transcription synthesizing up to 60% of cellular RNA. High level production relies on efficient binding initiation factors the promoter and recruitment Pol complexes containing factor Rrn3. Here, we determine cryo-EM structure I-Rrn3 complex at 7.5 Å resolution, compare it with Rrn3-free monomeric dimeric I. We observe that Rrn3 contacts A43/A14 stalk subunits A190 AC40, association re-organizes interaction interface,...
Orthomyxoviruses, such as influenza and thogotoviruses, are important human animal pathogens. Their segmented viral RNA genomes wrapped by nucleoproteins (NPs) into helical ribonucleoprotein complexes (RNPs). NP structures of several viruses have been reported. However, there still contradictory models how orthomyxovirus RNPs assembled. Here, we characterize the crystal structure Thogoto virus (THOV) found striking similarities to NPs, including a two-lobed domain architecture, positively...
Protein synthesis must be finely tuned in the developing nervous system as final essential step of gene expression. This study investigates architecture ribosomes from neocortex during neurogenesis, revealing Ebp1 a high-occupancy 60S peptide tunnel exit (TE) factor protein at near-atomic resolution by cryoelectron microscopy (cryo-EM). Ribosome profiling demonstrated Ebp1-60S binding is highest start codon initiation and N-terminal elongation, regulating ribosome occupancy these codons....
Viruses have evolved means to manipulate the host's ubiquitin-proteasome system, in order down-regulate antiviral host factors. The Vpx/Vpr family of lentiviral accessory proteins usurp substrate receptor DCAF1 Cullin4-RING ligases (CRL4), a modular ubiquitin involved DNA replication, repair and cell cycle regulation. CRL4DCAF1 specificity modulation by Vpx Vpr from certain simian immunodeficiency viruses (SIV) leads recruitment, poly-ubiquitylation subsequent proteasomal degradation...
SUMMARY Protein synthesis must be finely tuned in the nervous system, as it represents an essential feature of neurodevelopmental gene expression, and dominant pathology neurological disease. However, architecture ribosomal complexes developing mammalian brain has not been analyzed at high resolution. This study investigates ribosomes ex vivo from embryonic perinatal mouse neocortex, revealing Ebp1 a 60S peptide tunnel exit binding factor near-atomic resolution by multiparticle cryo-electron...
Bacteriophage λN protein, a paradigmatic anti-termination factor, binds nascent RNA and host Nus factors, rendering polymerase resistant to all pause termination signals. A 3.7 Å-resolution cryo-electron microscopy structure structure-informed functional analyses reveal an all-it-takes strategy, in which the intrinsically unstructured directly modifies interactions with nucleic acids subverts essential functions of NusA, NusE NusG reprogram transcriptional apparatus. repositions NusA...
Abstract Viruses have evolved means to manipulate the host’s ubiquitin-proteasome system, in order down-regulate antiviral host factors. The Vpx/Vpr family of lentiviral accessory proteins usurp substrate receptor DCAF1 Cullin4-RING ligases (CRL4), a modular ubiquitin involved DNA replication, repair and cell cycle regulation. CRL4 specificity modulation by Vpx Vpr from certain simian immunodeficiency viruses (SIV) leads recruitment, poly-ubiquitylation subsequent proteasomal degradation...