- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Viral Infections and Immunology Research
- HIV Research and Treatment
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Plant Virus Research Studies
- HIV/AIDS drug development and treatment
- RNA Interference and Gene Delivery
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Cytomegalovirus and herpesvirus research
- Plant Disease Resistance and Genetics
- Neurogenetic and Muscular Disorders Research
- Genetics and Neurodevelopmental Disorders
- Fungal and yeast genetics research
- Autism Spectrum Disorder Research
- Signaling Pathways in Disease
- MicroRNA in disease regulation
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- Influenza Virus Research Studies
- Mitochondrial Function and Pathology
Institute of Bioorganic Chemistry, Polish Academy of Sciences
2008-2022
Polish Academy of Sciences
2013-2017
Multidisciplinary Digital Publishing Institute (Switzerland)
2017
University of Georgia
2012-2017
Whitehead Institute for Biomedical Research
2017
Massachusetts Institute of Technology
2017
Marine Biological Laboratory
2017
University of California, Davis
2017
Frederick National Laboratory for Cancer Research
2013-2014
National Cancer Institute
2013-2014
Understanding the numerous functions that RNAs play in living cells depends critically on knowledge of their three-dimensional structure. Due to difficulties experimentally assessing structures large RNAs, there is currently great demand for new high-resolution structure prediction methods. We present novel method fully automated RNA 3D from a user-defined secondary The concept founded machine translation system. engine operates FRABASE database tailored dictionary relating and tertiary...
This paper is a report of second round RNA-Puzzles, collective and blind experiment in three-dimensional (3D) RNA structure prediction. Three puzzles, Puzzles 5, 6, 10, represented sequences three large structures with limited or no homology previously solved molecules. A lariat-capping ribozyme, as well riboswitches complexed to adenosylcobalamin tRNA, were predicted by seven groups using RNAComposer, ModeRNA/SimRNA, Vfold, Rosetta, DMD, MC-Fold, 3dRNA, AMBER refinement. Some derived models...
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...
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...
Ty1, a long terminal repeat retrotransposon of Saccharomyces, is structurally and functionally related to retroviruses. However, differentiating aspect between these retroelements the diversity replication strategies used by retrotransposons. To understand structural organization cis-acting elements present on Ty1 genomic RNA from GAG region that control reverse transcription, we applied chemoenzymatic probing RNA/tRNA complexes assembled in vitro virus-like particles. By comparing different...
Ty1 retrotransposon RNA has the potential to fold into a variety of distinct structures, mutation which affects retrotransposition frequencies. We show here that one functional structure is located at 5′ end genome and can assume pseudoknot conformation. Chemoenzymatic probing wild-type mutant mini-Ty1 RNAs supports existence such structure, while molecular genetic analyses mutations disrupting formation interfere with retrotransposition, indicating it provides critical biological function....
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...
Journal Article The HIV-2 Rev-response element: determining secondary structure and defining folding intermediates Get access Sabrina Lusvarghi, Lusvarghi 1HIV Drug Resistance Program, Reverse Transcriptase Biochemistry Section, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA 2Chemical Biology Laboratory, Search other works by this author on: Oxford Academic PubMed Google Scholar Joanna Sztuba-Solinska, Sztuba-Solinska Katarzyna J. Purzycka, Purzycka Gary T....
Retrovirus replication requires specialized transport mechanisms to export genomic mRNA from the nucleus cytoplasm of infected cell. This regulation is mediated by a combination viral and/or cellular factors that interact with cis-acting RNA elements linking CRM1 or NXF1 nuclear pathways. Endogenous type D murine LTR retrotransposons (musD) were reported contain an element located upstream 3'-LTR. Although functionally equivalent, musD element, termed distinct other retroviral elements, such...
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...
Understanding the function of RNA involved in biological processes requires a thorough knowledge structure. Toward this end, methodology dubbed "high-throughput selective 2' hydroxyl acylation analyzed by primer extension", or SHAPE, allows prediction secondary structure with single nucleotide resolution. This approach utilizes chemical probing agents that preferentially acylate stranded flexible regions aqueous solution. Sites modification are detected reverse transcription modified RNA,...
Post-transcriptional regulatory mechanisms of several complex and simple retroviruses retroelements have been elucidated, with the exception gammaretrovirus family. We found that, similar to other retroviruses, gag gene expression MuLV XMRV depends on post-transcriptional regulation mediated via an RNA sequence overlapping pro-pol open reading frame, termed Post-Transcriptional Element (PTE). PTE function can be replaced by heterologous export elements, e.g. CTE simian type D retroviruses....
Abstract The ribosomal core is universally conserved across the tree of life. However, eukaryotic ribosomes contain diverse rRNA expansion segments (ESs) on their surfaces. Sites ES insertions are predicted from sites insertion micro-ESs in archaea. Expansion segment 7 (ES7) one most regions ribosome, emanating a short stem loop and ranging to over 750 nucleotides mammals. We present secondary full-atom 3D structures ES7 species spanning diversity. Our results based experimental structures,...
Diversity in eukaryotic rRNA structure and function offers possibilities of therapeutic targets. Unlike ribosomes prokaryotes, contain species-specific expansion segments (ESs) with idiosyncratic structures functions that are essential specific to some organisms. Here we investigate segment 7 (ES7), one the largest most variable expansions ribosome. We hypothesize ES7 pathogenic fungi Candida albicans (ES7CA) could be a prototypic drug target. show isolated ES7CA folds reversibly native-like...
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 long-terminal repeat retrotransposon Ty1 is the most abundant mobile genetic element in many Saccharomyces cerevisiae isolates. retrotransposons contribute to diversity of host cells, but they can also act as an insertional mutagen and cause instability. Interestingly, retrotransposition occurs at a low level despite high RNA, even though S. lacks intrinsic defense mechanisms that other eukaryotes use prevent transposon movement. p22 recently discovered protein inhibits dose-dependent...
Recently, it has been reported that HIV-1 TAR RNA element releases functionally competent miRNAs upon processing by Dicer enzyme. Here, we extend the analysis of miRNA viral-encoding potential to TARRNA HIV-2. Using in vitro cleavages and computer-aided have found 124-mer domain, present at 5′ end HIV-2mRNAs, putatively encodes pre-miRNAs. When deduced sequences viral-encoded were matched against database human mRNA 3′-UTRs, appeared two candidates may target a large number cellular transcripts.
The long-terminal repeat (LTR)-retrotransposon Ty1 is a mobile genetic element that replicates through an RNA intermediate. Retroelement genomic transcripts contain internal structures fundamental to gene expression and propagation. In addition, long non-coding antisense RNAs overlap the 5'-terminal region of confer post-translational copy number control. Although LTR- retrotransposons are functionally related retroviruses, little known about structural determinants required for packaging or...