A5070130239- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- RNA regulation and disease
- HIV Research and Treatment
- Viral Infections and Immunology Research
- CRISPR and Genetic Engineering
- Plant Virus Research Studies
- Plant Disease Resistance and Genetics
- Protein Structure and Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Chemical Synthesis and Analysis
- Fungal and yeast genetics research
- Genomics and Phylogenetic Studies
- Cytomegalovirus and herpesvirus research
- Autism Spectrum Disorder Research
- Viral gastroenteritis research and epidemiology
- interferon and immune responses
- Genetics and Neurodevelopmental Disorders
- HIV/AIDS drug development and treatment
- Bacteriophages and microbial interactions
- Evolution and Genetic Dynamics
- Signaling Pathways in Disease
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2014-2024
Polish Academy of Sciences
2019
RNA-Puzzles is a collective experiment in blind 3D RNA structure prediction. We report here third round of RNA-Puzzles. Five puzzles, 4, 8, 12, 13, 14, all structures riboswitch aptamers and puzzle 7, ribozyme structure, are included this the experiment. The include biological binding sites for small molecules ( S -adenosyl methionine, cyclic diadenosine monophosphate, 5-amino 4-imidazole carboxamide riboside 5′-triphosphate, glutamine) proteins (YbxF), one set describes large conformational...
RNA-binding proteins regulate all aspects of RNA metabolism. Their association with is mediated by domains, which many remain uncharacterized. A recently reported example the NHL domain, found in prominent regulators cellular plasticity like C. elegans LIN-41. Here we employ an integrative approach to dissect specificity Using computational analysis, structural biology, and vivo studies worms human cells, find that a positively charged pocket, specific domain LIN-41 its homologs...
Ty1 Gag comprises the capsid of virus-like particles and provides nucleic acid chaperone (NAC) functions during retrotransposition in budding yeast. A subgenomic mRNA encodes a truncated protein (p22) that is cleaved by protease to form p18. p22/p18 strongly inhibits transposition can be considered an element-encoded restriction factor. Here, we show only p22 its short derivatives restrict mobility whereas other regions GAG inhibit weakly if at all. Mutational analyses suggest synthesized...
RNA is a unique biomolecule that involved in variety of fundamental biological functions, all which depend solely on its structure and dynamics. Since the experimental determination crystal structures laborious, computational 3D prediction methods are experiencing an ongoing thriving development. Such can lead to many models; thus, it necessary build comparisons extract common structural motifs for further medical or studies. Here, we introduce pipeline dedicated reference-free...
Abstract Matrix metalloproteinase 9 ( MMP ‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms been missing. In present study, we performed phenotype‐based genetic association study PGAS ) > 1,000 schizophrenia patients from Göttingen Research Association for Schizophrenia GRAS data collection and found an between ‐9 rs20544 C/T single‐nucleotide polymorphism SNP located 3′untranslated...
The TAR hairpin of the HIV-1 RNA genome is indispensable for trans-activation viral promoter and virus replication. structure has been studied extensively, but most attention directed at three-nucleotide bulge that constitutes binding site Tat protein. In contrast, conformational properties apical loop have remained elusive. We performed biochemical studies molecular dynamics simulations, which indicate structured stabilized by a cross-loop base pair between residues C30 G34. Mutational...
RNA dimerization is an essential step in the retroviral life cycle. Dimerization and encapsidation signals, closely linked HIV-2, are located leader region. The SL1 motif nucleocapsid protein considered important for both processes. In this study, we show structure of HIV-2 (+1–560) captured as a loose dimer. Potential structural rearrangements within were studied. dimer form, strand exists vitro single global fold. Two kissing loop interfaces identified: SL1/SL1 TAR/TAR. Evidence these...
The Gag polyprotein is a multifunctional regulator of retroviral replication and major structural component immature virions. nucleic acid chaperone (NAC) activity considered necessary to functions, but so far, NAC has only been confirmed for HIV-1 RSV polyproteins. nucleocapsid (NC) domain proposed be crucial interactions with acids activity. function matrix (MA) targeting binding the plasma membrane MA can also interact RNA influence Gag. Here, we characterize properties HIV-2 Gag, lacking...
RNAs adopt specific structures to perform their functions, which are critical fundamental cellular processes. For decades, these have been determined and modeled with strong support from computational methods. Still, the accuracy of latter ones depends on availability experimental data, for example, chemical probing information that can define pseudo-energy constraints RNA folding algorithms. At same time, diverse tools developed facilitate analysis visualization data structure experiments...
During replication of long terminal repeat (LTR)-retrotransposons, their proteins and genome (g) RNA assemble into virus-like particles (VLPs) that are not infectious but functionally related to retroviral virions. Both virions VLPs contain gRNA in a dimeric form, contrary retroviruses, little is known about how dimerization packaging occurs LTR-retrotransposons. The LTR-retrotransposon Ty1 from Saccharomyces cerevisiae an informative model for studying retrovirus replication. Using...
The HIV-2 TAR RNA domain (TAR-2) plays a key role in the trans -activation of transcription as it is target for Tat-2 protein and several cell factors. Here, we show that TAR-2 exists vitro two global, alternative forms: new, extended hairpin form with conformers already proposed branched hairpins form. This points strongly to structural polymorphism 5′ end leader RNA. evidence comes from non-denaturing PAGE mobility assay, 2D structure prediction, enzymatic Pb 2+ - or Mg -induced cleavages....
The nucleocapsid domain of Gag and mature protein (NC) act as nucleic acid chaperones facilitate folding acids at critical steps retroviral replication cycle. basic N-terminus HIV-1 NC was shown most important for the chaperone activity. HIV-2 (NCp8) (NCp7) proteins possess two highly conserved zinc fingers, flanked by residues. However, NCp8 N-terminal is significantly shorter contains less positively charged This study characterizes previously unknown, activity protein. We have...
Long terminal repeat (LTR)-retrotransposons constitute a significant part of eukaryotic genomes and influence their function evolution. Like other RNA viruses, LTR-retrotransposons efficiently utilize genome to interact with host cell machinery during replication. Here, we provide the first genome-wide secondary structure model for LTR-retrotransposon in living cells. Using SHAPE probing, explore yeast Ty1 retrotransposon its native vivo state under defined vitro conditions. Comparative...
Abstract Long terminal repeat (LTR)-retrotransposons are significant contributors to the evolution and diversity of eukaryotic genomes. Their RNA genomes (gRNA) serve as a template for protein synthesis reverse transcription DNA copy, which can integrate into host genome. Here, we used SHAPE-MaP strategy explore Ty3 retrotransposon gRNA structure in yeast under cell-free conditions. Our study reveals structural dynamics well-folded core, formed independently cellular environment. Based on...
The long terminal repeat (LTR) and non-LTR retrotransposons comprise approximately half of the human genome, we are only beginning to understand their influence on genome function evolution. LTR retrotransposon Ty1 is most abundant mobile genetic element in S. cerevisiae reference genome. replicates via an RNA intermediate shares several important structural functional characteristics with retroviruses. However, unlike retroviruses retrotransposition not infectious. Retrotransposons...
A universal feature of retroelement propagation is the formation distinct nucleoprotein complexes mediated by Gag capsid protein. The Ty1 retrotransposon protein from Saccharomyces cerevisiae lacks sequence homology with retroviral Gag, but functionally related. In addition to assembly functions, promotes RNA dimerization and cyclization initiation reverse transcription. Direct interactions between genomic (gRNA) are needed for replication, mutations in RNA-binding domain disrupt nucleation...
Abstract Regnase-1 is an evolutionarily conserved endoribonuclease. It degrades diverse mRNAs important for many biological processes including immune homeostasis, development and cancer. There are two competing models of Regnase-1-mediated mRNA silencing. One model postulates that works together with another RNA-binding protein, Roquin-1, which recruits to specific mRNAs. The other proposes the proteins function separately. Studying REGE-1, Caenorhabditis elegans ortholog Regnase-1, we have...
Abstract The outbreak of the COVID-19 pandemic has led to intensive studies both structure and replication mechanism SARS-CoV-2. In spite some secondary experiments being carried out, 3D key function regions viral RNA not yet been well understood. At beginning breakout, RNA-Puzzles community attempted envisage three-dimensional 5′- 3′-Un-Translated Regions (UTRs) SARS-CoV-2 genome. Here, we report results this prediction challenge, presenting methodologies developed by six participating...
The structural transitions RNAs undergo during trafficking are not well-understood. Here, we used the well-developed yeast Ty1 retrotransposon to provide first model of genome (g) RNA in nucleus from a retrovirus-like transposon. Through detailed comparison nuclear gRNA structure with those established cytoplasm, virus-like particles (VLPs), and synthesized vitro, detected alternations that occur retrotransposition. Full-length serves as mRNA for Gag Gag-Pol proteins is reverse transcribed...
The structural transitions RNAs undergo during trafficking are not well understood. Here, we used the well-developed yeast Ty1 retrotransposon to provide first model of genome (g) RNA in nucleus from a retrovirus-like transposon. Through detailed comparison nuclear gRNA structure with those established cytoplasm, virus-like particles (VLPs), and synthesized vitro, detected alterations that occur retrotransposition. Full-length serves as mRNA for Gag Gag-Pol proteins is reverse transcribed...