Group I Intron as a Potential Target for Antifungal Compounds: Development of a <i>Trans</i>-Splicing High-Throughput Screening Strategy
The search for safe and efficient new antifungal compounds for agriculture has led to more efforts in finding new modes of action. This involves the discovery of new molecular targets, including coding and non-coding RNA. Rarely found in plants and animals but present in fungi, group I introns are o...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/11/4460 |
| _version_ | 1827739330932637696 |
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| author | Bastien Malbert Virginie Labaurie Cécile Dorme Eric Paget |
| author_facet | Bastien Malbert Virginie Labaurie Cécile Dorme Eric Paget |
| author_sort | Bastien Malbert |
| collection | DOAJ |
| description | The search for safe and efficient new antifungal compounds for agriculture has led to more efforts in finding new modes of action. This involves the discovery of new molecular targets, including coding and non-coding RNA. Rarely found in plants and animals but present in fungi, group I introns are of interest as their complex tertiary structure may allow selective targeting using small molecules. In this work, we demonstrate that group I introns present in phytopathogenic fungi have a self-splicing activity in vitro that can be adapted in a high-throughput screening to find new antifungal compounds. Ten candidate introns from different filamentous fungi were tested and one group ID intron found in <i>F. oxysporum</i> showed high self-splicing efficiency in vitro. We designed the <i>Fusarium</i> intron to act as a <i>trans</i>-acting ribozyme and used a fluorescence-based reporter system to monitor its real time splicing activity. Together, these results are opening the way to study the druggability of such introns in crop pathogen and potentially discover small molecules selectively targeting group I introns in future high-throughput screenings. |
| first_indexed | 2024-03-11T03:01:17Z |
| format | Article |
| id | doaj.art-0c099044071241f18819ef5898002fef |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T03:01:17Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0c099044071241f18819ef5898002fef2023-11-18T08:16:55ZengMDPI AGMolecules1420-30492023-05-012811446010.3390/molecules28114460Group I Intron as a Potential Target for Antifungal Compounds: Development of a <i>Trans</i>-Splicing High-Throughput Screening StrategyBastien Malbert0Virginie Labaurie1Cécile Dorme2Eric Paget3Early Discovery, Biochemistry Excellence, Centre de Recherche La Dargoire, Bayer SAS, 69009 Lyon, FranceEarly Discovery, Biochemistry Excellence, Centre de Recherche La Dargoire, Bayer SAS, 69009 Lyon, FranceEarly Discovery, Biochemistry Excellence, Centre de Recherche La Dargoire, Bayer SAS, 69009 Lyon, FranceEarly Discovery, Biochemistry Excellence, Centre de Recherche La Dargoire, Bayer SAS, 69009 Lyon, FranceThe search for safe and efficient new antifungal compounds for agriculture has led to more efforts in finding new modes of action. This involves the discovery of new molecular targets, including coding and non-coding RNA. Rarely found in plants and animals but present in fungi, group I introns are of interest as their complex tertiary structure may allow selective targeting using small molecules. In this work, we demonstrate that group I introns present in phytopathogenic fungi have a self-splicing activity in vitro that can be adapted in a high-throughput screening to find new antifungal compounds. Ten candidate introns from different filamentous fungi were tested and one group ID intron found in <i>F. oxysporum</i> showed high self-splicing efficiency in vitro. We designed the <i>Fusarium</i> intron to act as a <i>trans</i>-acting ribozyme and used a fluorescence-based reporter system to monitor its real time splicing activity. Together, these results are opening the way to study the druggability of such introns in crop pathogen and potentially discover small molecules selectively targeting group I introns in future high-throughput screenings.https://www.mdpi.com/1420-3049/28/11/4460RNAself-splicinggroup IHTSribozyme<i>Fusarium</i> |
| spellingShingle | Bastien Malbert Virginie Labaurie Cécile Dorme Eric Paget Group I Intron as a Potential Target for Antifungal Compounds: Development of a <i>Trans</i>-Splicing High-Throughput Screening Strategy Molecules RNA self-splicing group I HTS ribozyme <i>Fusarium</i> |
| title | Group I Intron as a Potential Target for Antifungal Compounds: Development of a <i>Trans</i>-Splicing High-Throughput Screening Strategy |
| title_full | Group I Intron as a Potential Target for Antifungal Compounds: Development of a <i>Trans</i>-Splicing High-Throughput Screening Strategy |
| title_fullStr | Group I Intron as a Potential Target for Antifungal Compounds: Development of a <i>Trans</i>-Splicing High-Throughput Screening Strategy |
| title_full_unstemmed | Group I Intron as a Potential Target for Antifungal Compounds: Development of a <i>Trans</i>-Splicing High-Throughput Screening Strategy |
| title_short | Group I Intron as a Potential Target for Antifungal Compounds: Development of a <i>Trans</i>-Splicing High-Throughput Screening Strategy |
| title_sort | group i intron as a potential target for antifungal compounds development of a i trans i splicing high throughput screening strategy |
| topic | RNA self-splicing group I HTS ribozyme <i>Fusarium</i> |
| url | https://www.mdpi.com/1420-3049/28/11/4460 |
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