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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the Dermatophyte
Carlos H Lopes Rocha1, Flaviane M Galvão Rocha1, Pablo R Sanches1
1Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Background/Objectives:
Dermatophytosis, a prevalent fungal infection of keratinized tissues, is primarily caused by the filamentous fungus Trichophyton rubrum. Sertraline (SRT), an antidepressant with antifungal activity, has already demonstrated therapeutic potential against this fungus. Elucidating the effects of SRT may provide insights into its mechanism of action and fungal adaptation to this drug. Differential gene expression and alternative splicing (AS) facilitate fungal adaptations to various environmental conditions. This study aimed to provide a comprehensive overview of AS events and their implications in T. rubrum cultivated under sub-inhibitory concentrations of SRT.
Method:
The transcriptome of T. rubrum challenged with SRT was analyzed to detect AS events.
Results:
RNA-seq analysis revealed that SRT affected transcriptional and post-transcriptional events in numerous T. rubrum genes, including those encoding transcription factors, kinases, and efflux pumps. Among the AS events, intron retention was predominant. After 12 h of SRT exposure, intron-3 retention levels in the serine/arginine protein kinase mRNA transcripts were significantly increased compared with those in the control. This new isoform would produce a putative protein that partially lost its phosphotransferase domain.
Conclusions:
These findings highlight the potential mechanisms of action of SRT and suggest how T. rubrum adapts itself to this drug.
Insights
Sertraline (SRT) exposure alters gene expression and alternative splicing in Trichophyton rubrum, a common cause of fungal infections. Intron retention in serine/arginine protein kinase mRNA suggests a fungal adaptation mechanism to SRT.
Area of Science:
- Mycology
- Molecular Biology
- Pharmacology
Background:
- Dermatophytosis is a common fungal infection caused by *Trichophyton rubrum*.
- Sertraline (SRT), an antidepressant, exhibits antifungal properties against *T. rubrum*.
- Understanding SRT's effects and fungal adaptation is crucial for developing new treatments.
Purpose of the Study:
- To comprehensively analyze alternative splicing (AS) events in *T. rubrum* exposed to sub-inhibitory concentrations of SRT.
- To investigate the implications of AS in fungal adaptation to SRT.
- To elucidate the potential mechanisms of action of SRT against *T. rubrum*.
Main Methods:
- Transcriptome analysis of *T. rubrum* was performed using RNA-sequencing (RNA-seq).
- Differential gene expression and alternative splicing events were detected in SRT-treated samples.
- Specific AS events, such as intron retention, were quantified and analyzed.
Main Results:
- SRT significantly impacted transcriptional and post-transcriptional events in *T. rubrum*.
- Intron retention was the predominant AS event observed.
- Increased intron-3 retention in serine/arginine protein kinase mRNA was noted after 12h SRT exposure, potentially altering protein function.
Conclusions:
- SRT influences gene expression and alternative splicing in *T. rubrum*.
- Intron retention, particularly in serine/arginine protein kinase, represents a potential fungal adaptation strategy to SRT.
- These findings provide insights into SRT's antifungal mechanisms and *T. rubrum*'s response to the drug.
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