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Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.
ACS Chem Biol
January 2025
Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States.
We report the discovery of small molecules that target the RNA tertiary structure of self-splicing group II introns and display potent antifungal activity against yeasts, including the major public health threat . High-throughput screening efforts against a yeast group II intron resulted in an inhibitor class which was then synthetically optimized for enhanced inhibitory activity and antifungal efficacy. The most highly refined compounds in this series display strong, gene-specific antifungal activity against .
View Article and Find Full Text PDFProtein-free catalysis of DNA hydrolysis and self-integration by a ribozyme.
Nucleic Acids Res
January 2025
Biomimetic Chemistry, Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, Dortmund 44227, Germany.
Group II introns are ancient self-splicing ribozymes and retrotransposons. Though long speculated to have originated before translation, their dependence on intron-encoded proteins for splicing and mobility has cast doubt on this hypothesis. While some group II introns are known to retain part of their catalytic repertoire in the absence of protein cofactors, protein-free complete reverse splicing of a group II intron into a DNA target has never been demonstrated.
View Article and Find Full Text PDFDeveloping an enhanced chimeric permuted intron-exon system for circular RNA therapeutics.
Theranostics
September 2024
MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan 030001, China.
: Circular RNA (circRNA) therapeutics hold great promise as an iteration strategy in messenger RNA (mRNA) therapeutics due to their inherent stability and durable protein translation capability. Nevertheless, the efficiency of RNA circularization remains a significant constraint, particularly in establishing large-scale manufacturing processes for producing highly purified circRNAs. Hence, it is imperative to develop a universal and more efficient RNA circularization system when considering synthetic circRNAs as therapeutic agents with prospective clinical applications.
View Article and Find Full Text PDFsp. nov., a Novel Species of Entomopathogenic Fungi Associated with Weevils Impairing Coffee, Sugar Cane and Sweet Potato Cultivation.
J Fungi (Basel)
August 2024
Department of Biology, Technische Universität Darmstadt (TUDa), Schnittspahnstraße 10, 64287 Darmstadt, Germany.
Article Synopsis
- Research focuses on insect pathogenic fungi as eco-friendly alternatives to chemical insecticides, particularly in Cuba and Florida, where strains have been isolated from pests affecting coffee and sugar cane.* -
- A newly developed PCR method using ribosomal intergenic spacer (rIGS) sequences proves effective in distinguishing species within a complex, and it is enhanced with additional genetic markers.* -
- The findings characterize new fungal isolates associated with the coffee berry borer and propose these as a new taxon, demonstrating the utility of the rIGS-based PCR method for identifying new species in this context.*
In Vitro Self-Circularization Methods Based on Self-Splicing Ribozyme.
Int J Mol Sci
August 2024
R&D Center, Rznomics Inc., Seongnam 13486, Republic of Korea.
In vitro circular RNA (circRNA) preparation methods have been gaining a lot of attention recently as several reports suggest that circRNAs are more stable, with better performances in cells and in vivo, than linear RNAs in various biomedical applications. Self-splicing ribozymes are considered a major in vitro circRNA generation method for biomedical applications due to their simplicity and efficiency in the circularization of the gene of interest. This review summarizes, updates, and discusses the recently developed self-circularization methods based on the self-splicing ribozyme, such as group I and II intron ribozymes, and the pros and cons of each method in preparing circRNA in vitro.
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