ORCID Profile
0000-0002-4433-282X
Current Organisation
Flinders University
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Publisher: Portland Press Ltd.
Date: 12-04-2013
DOI: 10.1042/BJ20121761
Abstract: Hammerhead ribozyme is a versatile tool for down-regulation of gene expression in vivo. Owing to its small size and high activity, it is used as a model for RNA structure–function relationship studies. In the present paper we describe a new extended hammerhead ribozyme HH-2 with a tertiary stabilizing motif constructed on the basis of the tetraloop receptor sequence. This ribozyme is very active in living cells, but shows low activity in vitro. To understand it, we analysed tertiary structure models of substrate–ribozyme complexes. We calculated six unique catalytic core geometry parameters as distances and angles between particular atoms that we call the ribozyme fingerprint. A flanking sequence and tertiary motif change the geometry of the general base, general acid, nucleophile and leaving group. We found almost complete correlation between these parameters and the decrease of target gene expression in the cells. The tertiary structure model calculations allow us to predict ribozyme intracellular activity. Our approach could be widely adapted to characterize catalytic properties of other RNAs.
Publisher: MDPI AG
Date: 16-11-2020
DOI: 10.3390/CELLS9112488
Abstract: High-throughput RNA sequencing (RNA-seq) and dedicated bioinformatics pipelines have synergized to identify an expansive repertoire of unique circular RNAs (circRNAs), exceeding 100,000 variants. While the vast majority of these circRNAs comprise canonical exonic and intronic sequences, microexons (MEs)—which occur in 30% of functional mRNA transcripts—have been entirely overlooked. CircRNAs which contain these known MEs (ME-circRNAs) could be identified with commonly utilized circRNA prediction pipelines, CIRCexplorer2 and CIRI2, but were not previously recognized as ME-circRNAs. In addition, when employing a bespoke bioinformatics pipeline for identifying RNA chimeras, called Hyb, we could also identify over 2000 ME-circRNAs which contain novel MEs at their backsplice junctions, that are uncalled by either CIRCexplorer2 or CIRI2. Analysis of circRNA-seq datasets from gliomas of varying clinical grades compared with matched control tissue has shown circRNAs have potential as prognostic markers for stratifying tumor from healthy tissue. Furthermore, the abundance of microexon-containing circRNAs (ME-circRNAs) between tumor and normal tissues is correlated with the expression of a splicing associated factor, Serine/arginine repetitive matrix 4 (SRRM4). Overexpressing SRRM4, known for regulating ME inclusion in mRNAs critical for neural differentiation, in human HEK293 cells resulted in the biogenesis of over 2000 novel ME-circRNAs, including ME-circEIF4G3, and changes in the abundance of many canonical circRNAs, including circSETDB2 and circLRBA. This shows SRRM4, in which its expression is correlated with poor prognosis in gliomas, acts as a bona fide circRNA biogenesis factor. Given the known roles of MEs and circRNAs in oncogenesis, the identification of these previously unrecognized ME-circRNAs further increases the complexity and functional purview of this non-coding RNA family.
Publisher: MDPI AG
Date: 13-06-2019
DOI: 10.3390/CELLS8060583
Abstract: We address here organellar genetic regulation and intercompartment genome coordination. We developed earlier a strategy relying on a tRNA-like shuttle to mediate import of nuclear transgene-encoded custom RNAs into mitochondria in plants. In the present work, we used this strategy to drive trans-cleaving hammerhead ribozymes into the organelles, to knock down specific mitochondrial RNAs and analyze the regulatory impact. In a similar approach, the tRNA mimic was used to import into mitochondria in Arabidopsis thaliana the orf77, an RNA associated with cytoplasmic male sterility in maize and possessing sequence identities with the atp9 mitochondrial RNA. In both cases, inducible expression of the transgenes allowed to characterise early regulation and signaling responses triggered by these respective manipulations of the organellar transcriptome. The results imply that the mitochondrial transcriptome is tightly controlled by a “buffering” mechanism at the early and intermediate stages of plant development, a control that is released at later stages. On the other hand, high throughput analyses showed that knocking down a specific mitochondrial mRNA triggered a retrograde signaling and an anterograde nuclear transcriptome response involving a series of transcription factor genes and small RNAs. Our results strongly support transcriptome coordination mechanisms within the organelles and between the organelles and the nucleus.
Publisher: MDPI AG
Date: 11-06-2019
DOI: 10.3390/NCRNA5020040
Abstract: We are delighted to share with you our seventh Journal Club and highlight some of the most interesting papers published recently [...]
Publisher: Springer Science and Business Media LLC
Date: 10-09-2018
Publisher: Public Library of Science (PLoS)
Date: 29-01-2014
Publisher: Wiley
Date: 12-04-2023
DOI: 10.1002/WRNA.1786
Abstract: Ribonucleic acid (RNA) molecules are indispensable for cellular homeostasis in healthy and malignant cells. However, the functions of RNA extend well beyond that of a protein‐coding template. Rather, both coding and non‐coding RNA molecules function through critical interactions with a plethora of cellular molecules, including other RNAs, DNA, and proteins. Deconvoluting this RNA interactome, including the interacting partners, the nature of the interaction, and dynamic changes of these interactions in malignancies has yielded fundamental advances in knowledge and are emerging as a novel therapeutic strategy in cancer. Here, we present an RNA‐centric review of recent advances in the field of RNA–RNA, RNA–protein, and RNA–DNA interactomic network analysis and their impact across the Hallmarks of Cancer. This article is categorized under: RNA in Disease and Development RNA in Disease RNA Interactions with Proteins and Other Molecules RNA–Protein Complexes
Publisher: MDPI AG
Date: 11-06-2019
DOI: 10.3390/NCRNA5020040
Abstract: We are delighted to share with you our seventh Journal Club and highlight some of the most interesting papers published recently [...]
Publisher: Portland Press Ltd.
Date: 21-09-2015
DOI: 10.1042/BJ20150398
Abstract: Despite great progress in the treatment of AIDS, HIV-1 remains one of the major concerns as a human pathogen. One of the therapeutic strategies against viral infections is the application of catalytic ribonucleic acids (ribozymes) that can significantly reduce expression of a target gene by site-specific hydrolysis of its mRNA. In the present paper, we report a study on the activity of several variants of hammerhead ribozymes targeting a conserved region within mRNA encoding HIV-1 envelope glycoprotein gp41. On the basis of the data from in vitro assays and gene silencing in the cultured cells, we propose a new hammerhead ribozyme targeting the gp41-encoding sequence that can be potentially used as a therapeutic agent in AIDS treatment. Moreover, we demonstrate that the hydrolytic activity of the ribozyme in the intracellular environment cannot be inferred solely from the results of in vitro experiments.
Publisher: Polskie Towarzystwo Biochemiczne (Polish Biochemical Society)
Date: 04-03-2017
Abstract: Despite the wealth of data on RNA secondary structure, conformational dynamics and tertiary structure in vitro and in vivo, predicting RNA biological activity in cellular environments remains difficult. Here we describe a method of in silico RNA fingerprinting that allows efficient design of hammerhead ribozyme molecules with a high intracellular efficiency. Our method, which we call RNA dactyloscopy, is a reliable tool for assessing catalytic properties, modeling and design of RNA.
Publisher: Springer Berlin Heidelberg
Date: 2012
Publisher: American Society for Cell Biology (ASCB)
Date: 15-04-2021
Abstract: Working as a researcher is very satisfying. However, it comes with a price. This is a story about growing up as a scientist in the field of molecular biology. Starting as a young, rather naive researcher, I learned, step by step, not only the facts about my favorite RNA molecules but also the demands and downsides of academia. Going through my recent “scientific awakening,” I fully acknowledged the rules of the game: to write, to publish, to patent, to apply for grants and awards, and finally, to engage in all forms of coscientific endeavors. After going through a orce, single parenting, immigration, and being scooped, I became a scientist who finally takes her career in her own hands and navigates through, but does not succumb to, the difficulties in science. This is my monument to resilience.
Publisher: Cold Spring Harbor Laboratory
Date: 17-05-2021
DOI: 10.1101/2021.05.13.444021
Abstract: RNA homodimerization is important for various physiological processes, including the assembly of membraneless organelles, RNA subcellular localization, and packaging of viral genomes. However, understanding of RNA homodimerization has been h ered by the lack of systematic in vivo detection methods. Here we show that PARIS, COMRADES, and other RNA proximity ligation methods can detect RNA homodimers transcriptome-wide as “overlapping” chimeric reads that contain more than one copy of the same sequence. Analysing published proximity ligation datasets, we show that RNA:RNA homodimers mediated by direct base-pairing interactions are rare across the transcriptome, but highly enriched in specific transcripts, including U8 snoRNA, U2 snRNA and a subset of tRNAs. Analysis of data from virus-infected cells reveals homodimerization of SARS-CoV-2 and Zika genomes, mediated by specific palindromic sequences located within protein-coding regions of N protein in SARS-CoV-2 and NS2A gene in Zika. We speculate that regions of viral genomes involved in homodimerization may constitute effective targets for antiviral therapies.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Marta Gabryelska.