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• W3217732511 abstract "Fungal pathogens represent an expanding global health threat for which treatment options are limited. Self-splicing group II introns have emerged as promising drug targets, but their development has been limited by a lack of information on their distribution and architecture in pathogenic fungi. To meet this challenge, we developed a bioinformatic workflow for scanning sequence data to identify unique RNA structural signatures within group II introns. Using this approach, we discovered a set of ubiquitous introns within thermally dimorphic fungi (genera of Blastomyces, Coccidioides and Histoplasma). These introns are the most biochemically reactive group II introns ever reported, and they self-splice rapidly under near-physiological conditions without protein cofactors. Moreover, we demonstrated the small molecule targetability of these introns by showing that they can be inhibited by the FDA-approved drug mitoxantrone in vitro. Taken together, our results highlight the utility of structure-based informatic searches for identifying riboregulatory elements in pathogens, revealing a striking diversity of reactive self-splicing introns with great promise as antifungal drug targets." @default.
• W3217732511 created "2021-12-06" @default.
• W3217732511 creator A5001453445 @default.
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• W3217732511 date "2021-11-25" @default.
• W3217732511 modified "2023-09-23" @default.
• W3217732511 title "Discovery of highly reactive self-splicing group II introns within the mitochondrial genomes of human pathogenic fungi" @default.
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• W3217732511 doi "https://doi.org/10.1093/nar/gkab1077" @default.
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