- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- DNA Repair Mechanisms
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Heat shock proteins research
- Sulfur Compounds in Biology
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- Nitric Oxide and Endothelin Effects
- Ubiquitin and proteasome pathways
- Biochemical effects in animals
- thermodynamics and calorimetric analyses
- Amino Acid Enzymes and Metabolism
- Antibiotic Resistance in Bacteria
- Hemoglobin structure and function
- Enzyme Structure and Function
- Telomeres, Telomerase, and Senescence
- Polyamine Metabolism and Applications
- Genomics and Phylogenetic Studies
- Circadian rhythm and melatonin
New York University
2016-2025
NYU Langone Health
2002-2025
Howard Hughes Medical Institute
2015-2024
New York Proton Center
2012-2023
Institute of Cytology
2020
Russian Academy of Sciences
2020
Klinik für Frauenheilkunde
2020
München Klinik
2020
Klinikum rechts der Isar
2020
St Petersburg University
2020
Many prokaryotic species generate hydrogen sulfide (H(2)S) in their natural environments. However, the biochemistry and physiological role of this gas nonsulfur bacteria remain largely unknown. Here we demonstrate that inactivation putative cystathionine β-synthase, γ-lyase, or 3-mercaptopyruvate sulfurtransferase Bacillus anthracis, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli suppresses H(2)S production, rendering these pathogens highly sensitive to a multitude...
During transcription of protein-coding genes, bacterial RNA polymerase (RNAP) is closely followed by a ribosome that translates the newly synthesized transcript. Our in vivo measurements show overall elongation rate tightly controlled translation. Acceleration and deceleration result corresponding changes speed RNAP. Moreover, we found an inverse correlation between number rare codons gene, which delay progression, transcription. The stimulating effect on RNAP achieved preventing its...
Bacterial nitric oxide synthases (bNOS) are present in many Gram-positive species and have been demonstrated to synthesize NO from arginine vitro vivo. However, the physiological role of bNOS remains largely unknown. We show that generated by increases resistance bacteria a broad spectrum antibiotics, enabling survive share habitats with antibiotic-producing microorganisms. NO-mediated is achieved through both chemical modification toxic compounds alleviation oxidative stress imposed...
Transcription of the bacterial genome by RNA polymerase must terminate at specific points. can be terminated Rho factor, an essential protein in enterobacteria. We used antibiotic bicyclomycin, which inhibits Rho, to assess its role on a genome-wide scale. is revealed as global regulator gene expression that matches Escherichia coli transcription translational needs. also found genes E. are most repressed prophages and other horizontally acquired portions genome. Elimination these foreign...
Significance Hydrogen sulfide (H 2 S) is a highly toxic gas that interferes with cellular respiration; however, at low physiological amounts, it plays an important role in cell signaling. Remarkably, bacteria, endogenously produced H S has been recently recognized as general protective molecule, which renders multiple bacterial species resistant to oxidative stress and various classes of antibiotics. The mechanism this phenomenon remains poorly understood. In paper, we use Escherichia coli...
Misfolded luminal endoplasmic reticulum (ER) proteins undergo ER-associated degradation (ERAD-L): They are retrotranslocated into the cytosol, polyubiquitinated, and degraded by proteasome. ERAD-L is mediated Hrd1 complex (composed of Hrd1, Hrd3, Der1, Usa1, Yos9), but mechanism retrotranslocation remains mysterious. Here, we report a structure active complex, as determined cryo-electron microscopy analysis two subcomplexes. Hrd3 Yos9 jointly create binding site that recognizes glycosylated...
Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting bacterial hydrogen sulfide (H2S)-mediated defense system. We identified cystathionine γ-lyase (CSE) as primary generator H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, discovered small molecules that inhibit CSE. These inhibitors potentiate bactericidal against both pathogens vitro mouse models...
In bacteria, an intrinsic transcription termination signal appears in RNA as a hairpin followed by approximately eight uridines (U stretch) at the 3′ terminus. This leads to rapid dissociation of ternary elongation complex (TEC) into RNA, DNA, and polymerase. We demonstrate that inactivates then destabilizes TEC weakening interactions RNA–DNA hybrid–binding site RNA-binding hold together. Formation is restricted moment when reaches point depends upon melting four five hybrid base pairs...
Numerous sophisticated systems have been described that protect bacteria from increased levels of reactive oxygen species. Although indispensable during prolonged oxidative stress, these response depend on newly synthesized proteins, and are hence both time energy consuming. Here, we describe an “express” cytoprotective system in Bacillus subtilis which depends nitric oxide (NO). We show NO immediately protects bacterial cells species by two independent mechanisms. transiently suppresses the...
Many operons in Gram-positive bacteria that are involved methionine (Met) and cysteine (Cys) biosynthesis possess an evolutionarily conserved regulatory leader sequence (S-box) positively controls these genes response to starvation. Here, we demonstrate a feed-back regulation mechanism utilizes S -adenosyl-methionine as effector. directly specifically binds the nascent S-box RNA, causing intrinsic terminator form interrupt transcription prematurely. The RNA thus expands family of newly...
Transcription elongation is responsible for rapid synthesis of RNA chains thousands nucleotides in vivo. In contrast, a single round transcription performed vitro frequently interrupted by pauses and arrests that drastically reduce the rate yield full-length transcript. Here we demonstrate most transcriptional delays disappear if more than one polymerase (RNAP) molecule initiates from same promoter. Anti-arrest anti-pause effects trailing RNAP are due to forward translocation leading...
Newly synthesized proteins aggregate extensively in Escherichia coli rpoH mutants, which are deficient the heat shock (hsp). Overproduction of either GroEL and GroES or DnaK DnaJ prevents aggregation. If expressed together, four hsp effective at physiological concentrations. Our data suggest that have complementary functions folding assembly most proteins.