A5044820537- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Advanced biosensing and bioanalysis techniques
- Genetic diversity and population structure
- Viral Infections and Immunology Research
- DNA and Nucleic Acid Chemistry
- Molecular Biology Techniques and Applications
- Polyamine Metabolism and Applications
- Cancer-related gene regulation
- Protist diversity and phylogeny
- Genetic Mapping and Diversity in Plants and Animals
- Bacteriophages and microbial interactions
- Endoplasmic Reticulum Stress and Disease
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Biochemical and Molecular Research
- Bacterial Genetics and Biotechnology
- Epigenetics and DNA Methylation
- Nuclear Receptors and Signaling
- Animal Genetics and Reproduction
Engelhardt Institute of Molecular Biology
2014-2025
Genetic Technologies (Australia)
2025
Moscow Institute of Physics and Technology
2024
Research Centre for Medical Genetics
2021
Russian Academy of Sciences
2011
Lomonosov Moscow State University
2010
Institute of Cytology and Genetics
2002-2008
Siberian Branch of the Russian Academy of Sciences
2008
SUNY Downstate Health Sciences University
2006
Kunming Institute of Zoology
2003
Poly(A)-binding protein (PABP) is a major component of the messenger RNA–protein complex. PABP able to bind poly(A) tail mRNA, as well translation initiation factor 4G and eukaryotic release 3a (eRF3a). has been found stimulate inhibit nonsense-mediated mRNA decay. Using reconstituted mammalian in vitro system, we show that directly stimulates termination. increases efficiency termination by recruitment eRF3a eRF1 ribosome. PABP's function depends on its C-terminal domain interaction with...
Efficient stop codon recognition and peptidyl-tRNA hydrolysis are essential in order to terminate translational elongation maintain protein sequence fidelity. Eukaryotic termination is mediated by a release factor complex that includes eukaryotic 1 (eRF1) eRF3. The N terminus of eRF1 contains highly conserved motifs couple at the ribosomal A site hydrolysis. We reveal Jumonji domain-containing 4 (Jmjd4), 2-oxoglutarate- Fe(II)-dependent oxygenase, catalyzes carbon (C4) lysyl hydroxylation...
Eukaryotic translation initiation is tightly regulated, requiring a set of conserved factors (eIFs). Translation capped mRNA depends on the trimeric eIF4F complex and eIF4B to load onto 43S pre-initiation comprising 40S 1, 1A, 2, 3 5 as well initiator-tRNA. Binding followed by scanning in 48S complex, until start codon recognised. Here, we use reconstituted system prepare human complexes assembled presence eIF4F. The highly purified h-48S are used for cross-linking/mass spectrometry,...
Abstract The poly(A) tail plays an important role in maintaining mRNA stability and influences translation efficiency via binding with PABP. However, the impact of length on remains incompletely understood. This study explores effects human translation. We determined rates cell lysates using mRNAs different tails. Cap-dependent was stimulated by tail, however, it largely independent length, exception observed case 75 nt tail. Conversely, cap-independent displayed a positive correlation...
The Afrotheria, a supraordinal grouping of mammals whose radiation is rooted in Africa, strongly supported by DNA sequence data but not their disparate anatomical features. We have used flow-sorted human, aardvark, and African elephant chromosome painting probes applied reciprocal schemes to representatives two the Afrotherian orders, Tubulidentata (aardvark) Proboscidea (elephants), an attempt shed additional light on evolutionary affinities this enigmatic group mammals. Although we yet...
Release factor eRF1 plays a key role in the termination of protein synthesis eukaryotes. The consists three domains (N, M and C) that perform unique roles termination. Previous studies point mutants standard/variant code chimeras unequivocally demonstrated direct involvement highly conserved N-domain motifs (NIKS, YxCxxxF GTx) stop codon recognition. In current study, we extend this work by investigating 41 invariant residues decoding human eRF1. Using combination conservative...
The human DEAD-box RNA-helicase DDX19 functions in mRNA export through the nuclear pore complex. yeast homolog of this protein, Dbp5, has been reported to participate translation termination. Using a reconstituted mammalian vitro system, we show that protein is also important for It associated with fraction translating ribosomes. We interacts pre-termination complexes (preTCs) nucleotide-dependent manner. Furthermore, increases efficiency termination complex (TC) formation and peptide...
Polyadenylate-binding protein (PABP) stimulates translation termination via interaction of its C-terminal domain with eukaryotic polypeptide chain release factor, eRF3. Additionally, two other proteins, poly(A)-binding protein-interacting proteins 1 and 2 (PAIP1 PAIP2), bind the same PABP regulate translation-related activity. To study biochemistry eRF3 PAIP1/2 competition for binding, we quantified effects PAIPs on in presence or absence PABP. Our results demonstrated that both PAIP1 PAIP2...
The nucleotide context surrounding stop codons significantly affects the efficiency of translation termination. In eukaryotes, various 3′ contexts that are unfavorable for termination have been described; however, exact molecular mechanism mediates their effects remains unknown. this study, we used a reconstituted mammalian system to examine in different contexts, including several previously described weak codon contexts. We developed an approach estimate level readthrough absence...
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system is a revolutionary tool for precise genome editing across various cell types. Ribonucleoproteins (RNPs), encompassing the Cas9 protein and guide RNA (gRNA), have emerged as promising technique due to their increased specificity reduced off-target effects. This method eliminates need plasmid DNA introduction, thereby preventing potential integration of foreign into target genome. Given requirement large...
Eukaryotic translation initiation factor 4F (eIF4F), comprising subunits eIF4G, eIF4E, and eIF4A, plays a pivotal role in the 48S preinitiation complex assembly ribosomal scanning. Additionally, eIF4B enhances helicase activity of eIF4A. eIF4F also interacts with poly (A)-binding protein (PABP) bound to (A) tail messenger RNA (mRNA), thereby forming closed-loop structure. PABP, turn, eukaryotic release 3 (eRF3), stimulating termination. Here, we employed reconstituted mammalian system...
Inhibition of primer extension by ribosome–mRNA complexes (toeprinting) is a proven and powerful technique for studying mechanisms mRNA translation. Here we have assayed an advanced toeprinting approach that employs fluorescently labeled DNA primers, followed capillary electrophoresis utilizing standard instruments sequencing fragment analysis. We demonstrate this improved not merely fast cost-effective, but also brings the inhibition method up to next level. The electrophoretic pattern...
In eukaryotes a single class-1 translation termination factor eRF1 decodes the three stop codons: UAA, UAG and UGA. Some ciliates, like Euplotes , have variant code, here eRF1s exhibit UAR-only specificity, whereas UGA is reassigned as sense codon. Since eukaryote stop-codon recognition associated with its N-terminal domain, structural features should exist in N domain of ciliate that restrict their specificity. Using an vitro reconstituted eukaryotic system we demonstrate chimeric composed...
The human genome contains about 1.5 million Alu elements, which are transcribed into RNAs by RNA polymerase III.Their expression is upregulated following stress and viral infection, they associate with the SRP9/14 protein dimer in cytoplasm forming RNPs.Using cell-free translation, we have previously shown that RNPs inhibit polysome formation.Here, describe mechanism of RNP-mediated inhibition translation initiation demonstrate its effect on cellular RNAs.Both cap-dependent IRES-mediated...
Nsp1 of SARS-CoV-2 regulates the translation host and viral mRNAs in cells. inhibits initiation by occluding entry channel 40S ribosome subunit. The structural study Nsp1-ribosomal complexes reported post-termination 80S complex containing Nsp1, eRF1 ABCE1. Considering presence ribosomal complex, we hypothesized that may be involved termination. Using a cell-free system reconstituted vitro system, show stimulates peptide release formation termination complexes. Detailed analysis activity...
ABSTRACT Nonsense variants underlie many genetic diseases. The phenotypic impact of nonsense is determined by nonsense-mediated mRNA decay (NMD), which degrades transcripts with premature termination codons (PTCs). Despite its clinical importance, the factors controlling transcript-specific and context-dependent variation in NMD activity remain poorly understood. Through analysis human datasets, we discovered that amino acid preceding PTC strongly influences activity. Notably, glycine...
Although some data link archaeal and eukaryotic translation, the overall mechanism of protein synthesis in archaea remains largely obscure. Both (aRF1) (eRF1) single release factors recognize all three stop codons. The genus Methanosarcinaceae contains two aRF1 homologs, also uses UAG to encode 22nd amino acid, pyrrolysine. Here we provide an analysis last stage translation pyrrolysine‐utilizing species. We demonstrated that only one Methanosarcina barkeri homologs possesses activity...
Multidirectional comparative chromosome painting was used to investigate the karyotypic relationships among representative species from three Feliformia families of order Carnivora (Viverridae, Hyaenidae and Felidae). Complete sets probes derived flow-sorted chromosomes domestic dog, American mink, human were hybridized onto metaphases spotted hyena (<i>Crocuta crocuta</i>, 2n = 40) masked palm civet (<i>Paguma larvata</i>, 44). Extensive chromosomal conservation is...
Termination of translation in eukaryotes is triggered by two polypeptide chain release factors, eukaryotic class 1 factor (eRF1) and 2 3. eRF1 a three‐domain protein that interacts with 3 via its C‐terminal domain (C‐domain). The high‐resolution NMR structure the human C‐domain (residues 277–437) has been determined solution. overall fold β‐strand core solution are similar to those found crystal structure. minidomain 329–372), which was ill‐defined structure, backbone dynamics, studied using...
Stabilization of the ribosomal complexes plays an important role in translational control. Mechanisms ribosome stabilization have been studied detail for initiation and elongation eukaryotic translation, but almost nothing is known about termination complexes. Here, we present one mechanisms fine-tuning translation process eukaryotes. We show that certain deacylated tRNAs, remaining E site at end cycle, increase stability posttermination Moreover, only part eRF1 recognizing stop codon...