A5090152625- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- DNA Repair Mechanisms
- Water Treatment and Disinfection
- Folate and B Vitamins Research
- Pharmaceutical and Antibiotic Environmental Impacts
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Salmonella and Campylobacter epidemiology
- Endoplasmic Reticulum Stress and Disease
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Toxin Mechanisms and Immunotoxins
- Genetic factors in colorectal cancer
- Vibrio bacteria research studies
- Molecular Biology Techniques and Applications
- Nuclear Structure and Function
- Polyamine Metabolism and Applications
BioTechMed-Graz
2017-2024
University of Graz
2013-2024
Graz University of Technology
2019
Heidelberg University
2008-2009
Many RNA nucleases and helicases participate in ribosome biogenesis, but how they cooperate with each other is largely unknown. Here we report that vivo cleavage of the yeast pre-rRNA at site D, 3'-end 18 S rRNA, requires functional interactions between PIN (PilT N terminus) domain protein Nob1 DEAH box helicase Prp43. showed specific on a D-site substrate analogue vitro, which was abolished by mutations or substrate. Genetic analyses linked to late pre-40 S-associated factor Ltv1, Prp43,...
Formation of eukaryotic ribosomes is driven by energy-consuming enzymes. The AAA-ATPase Drg1 essential for the release several shuttling proteins from cytoplasmic pre-60S particles and loading late joining proteins. However, its exact role in ribosome biogenesis has been unknown. Here we show that protein Rlp24 recruited to stimulated ATPase activity. ATP hydrolysis second AAA domain was required In vitro, specifically exclusively extracted purified particles. promoted interaction with...
Abstract Eukaryotic ribosomes assemble by association of ribosomal RNA with proteins into nuclear precursor particles, which undergo a complex maturation pathway coordinated non-ribosomal assembly factors. Here, we provide functional insights how successive structural re-arrangements in protein S3 promote the 40S subunit. We show that dimerizes and is imported nucleus its N-domain rotated conformation associated chaperone Yar1. Initial precursors occurs via C-domain, while protrudes from...
Quantitative information about the levels and dynamics of post-translational modifications (PTMs) is critical for an understanding cellular functions. Protein arginine methylation (ArgMet) important subclass PTMs involved in a plethora (patho)physiological processes. However, because lack methods global analysis ArgMet, link between ArgMet levels, dynamics, (patho)physiology remains largely unknown. We utilized high sensitivity robustness nuclear magnetic resonance (NMR) spectroscopy to...
Allelic forms of DRG1/AFG2 confer resistance to the drug diazaborine, an inhibitor ribosome biogenesis in Saccharomyces cerevisiae. Our results show that AAA-ATPase Drg1 is essential for 60S maturation and associates with precursor particles cytoplasm. Functional inactivation leads increased cytoplasmic localization shuttling pre-60S factors like Rlp24, Arx1, Tif6. Surprisingly, Nog1, a nuclear factor, was also relocalized cytoplasm under these conditions, suggesting it previously...
Ribosome biogenesis takes place successively in the nucleolar, nucleoplasmic, and cytoplasmic compartments. Numerous nonribosomal factors transiently associate with nascent ribosomes, but mechanisms driving ribosome formation are mostly unknown. Here, we show that an energy-consuming enzyme, AAA-type (ATPases associated various cellular activities) ATPase Rix7, restructures a novel pre-60S particle at transition from nucleolus to nucleoplasm. Rix7 interacts genetically Nsa1 is targeted...
For some time now, antibiotic-resistant bacterial strains have been found in the human population, foods, livestock and wild animals, as well surface waters. The entry of antibiotics resistant into environment plays an important role spread antibiotic resistance. goal present study was to monitor resistances through contamination wastewater. To assess extent transmission from sources environment, resistance patterns Escherichia coli isolated patients compared those sewage sludge. Our results...
2000 ribosomes have to be synthesized in yeast every minute. Therefore the fast production of ribosomal proteins, their efficient delivery nucleus and correct incorporation into subunits are prerequisites for optimal growth rates. Here, we report that ankyrin repeat protein Yar1 directly interacts with small subunit Rps3 accompanies newly from cytoplasm where is assembled pre-ribosomal subunits. A yar1 deletion strain displays a similar phenotype as an rps3 mutant strain, showing...
The drug diazaborine is the only known inhibitor of ribosome biogenesis and specifically blocks large subunit formation in eukaryotic cells. However, target this mechanism inhibition were unknown. Here we identify AAA-ATPase Drg1 as a diazaborine. Inhibitor binding into second AAA domain requires ATP loading results hydrolysis site. As consequence physiological activity Drg1, i.e. release Rlp24 from pre-60S particles, blocked, further progression cytoplasmic preribosome maturation prevented....
Ribosome biogenesis is a central process in every growing cell. In eukaryotes, it requires more than 250 non-ribosomal assembly factors, most of which are essential. Despite this large repertoire potential targets, only very few chemical inhibitors ribosome known so far. Such valuable tools to study highly dynamic and elucidate mechanistic details individual maturation steps. Moreover, particular importance for fast proliferating cells, suggesting its inhibition could be valid strategy...
Abstract Eukaryotic ribosomes are synthesized in a hierarchical process driven by plethora of assembly factors, but how maturation events at physically distant sites on pre-ribosomes coordinated is poorly understood. Using functional analyses and cryo-EM, we show that ribosomal protein Rps20 orchestrates communication between two multi-step across the pre-40S subunit. Our study reveals during maturation, formation essential contacts Rps3 permits factor Ltv1 to recruit Hrr25 kinase, thereby...
Colorectal cancer (CRC) is the third most common cause of related death worldwide. Furthermore, with more than 1.2 million cases registered per year, it constitutes frequent diagnosed entity Deregulation protein synthesis has received considerable attention as a major step in development and progression. Eukaryotic translation initiation factors (eIFs) are involved regulation functionally linked to phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) signaling pathway....
Dedicated chaperones protect newly synthesized ribosomal proteins (r-proteins) from aggregation and accompany them on their way to assembly into nascent ribosomes. Currently, only nine of the ∼80 eukaryotic r-proteins are known be guarded by such chaperones. In search new dedicated r-protein chaperones, we performed a tandem-affinity purification based screen looked for factors co-enriched with individual small subunit r-proteins. We report identification Nap1 Tsr4 as direct binding partners...
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Dysregulation protein synthesis plays a major role in carcinogenesis, process regulated at multiple levels, including translation mRNA into proteins. Ribosome assembly requires correct association ribosome subunits, which ensured by eukaryotic initiation factors (eIFs). eIFs have become targets therapy studies, and promising data on eIF6 various entities been reported. Therefore, we hypothesised that...
After their cytoplasmic synthesis, ribosomal proteins need to be transported into the nucleus, where they assemble with RNA pre-ribosomal particles. Due physicochemical properties, protection from aggregation on this path. Newly synthesized protein Rps3 forms a dimer that is associated one molecule of its specific chaperone Yar1. Here we report redundant pathways contribute nuclear import Rps3, classical importin α/β pathway (Kap60/Kap95 in yeast) constituting main route. The Kap60/Kap95...
Diazaborine treatment of yeast cells was shown previously to cause accumulation aberrant, 3'-elongated mRNAs. Here we demonstrate that the drug inhibits maturation rRNAs for large ribosomal subunit. Pulse-chase analyses showed processing 27S pre-rRNA consecutive species blocked in drug-treated wild-type strain. The steady-state level 7S clearly reduced after short-term with inhibitor. At same time an increase 35S observed. Longer incubation inhibitor resulted a decrease precursor. Primer...
Our results suggest that IκBα sequesters not only p65 but also RPS3 in the cytoplasm. This would ensure maintenance of an pool for NF‐κB pathway as well equimolar release and upon stimulation.
The formation of ribosomal subunits is a highly dynamic process that initiated in the nucleus and involves more than 200 trans-acting factors, some which accompany pre-ribosomes into cytoplasm have to be recycled nucleus. inhibitor diazaborine prevents cytoplasmic release recycling shuttling pre-60S maturation factors by inhibiting AAA-ATPase Drg1. failure recycle these proteins results their depletion nucleolus halts pathway at an early step. Here, we made use fast onset inhibition chase...
Enzymes containing the FIC (filamentation induced by cyclic AMP) domain catalyze post-translational modifications of target proteins. In bacteria activity some Fic proteins resembles classical toxin-antitoxin (TA) systems. An excess toxin over neutralizing antitoxin can enable to survive stress conditions slowing metabolic processes and promoting dormancy. The cell return normal growth when sufficient is present block activity. genes human animal pathogen Campylobacter fetus are...
Eukaryotic ribosome synthesis involves more than 200 assembly factors, which promote ribosomal RNA (rRNA) processing, modification and folding, of proteins. The formation maturation the earliest pre-60S particles requires structural remodeling by Npa1 complex, but is otherwise still poorly understood. Here, we introduce Rbp95 (Ycr016w), a constituent early particles, as novel factor. We show that both genetically physically linked to most complex members protein Rpl3. demonstrate an...