# Alternative Splicing Analysis Revealed That the Transcription Factor PacC Shapes the Virulence of the Dermatophyte Trichophyton interdigitale

## TL;DR

The study shows that the transcription factor PacC controls alternative splicing in the fungus Trichophyton interdigitale, which is important for its ability to cause infection.

## Contribution

This work identifies PacC as a key regulator of alternative splicing and virulence in the dermatophyte Trichophyton interdigitale.

## Key findings

- RNA-seq analysis of a ΔpacC mutant revealed intron retention events affecting genes related to ion transport, metabolism, and genome maintenance.
- PacC-dependent alternative splicing generated isoforms of proteins involved in cytoskeleton and metabolism, potentially impacting infection processes.
- Exon-skipping in RSC1 suggests PacC's role in epigenetic regulation under host-like conditions.

## Abstract

Rapid responses to environmental changes are essential for maintaining fitness. In pathogenic fungi such as the dermatophyte Trichophyton interdigitale, appropriate responses to environmental shifts determine successful infection. Transcriptional regulation and alternative splicing (AS) are key modulators of fungal adaptation and pathogenesis. Here, we validated the role of the transcription factor PacC in coordinating AS in T. interdigitale grown in infection-mimicking medium. RNA-seq analysis of a ΔpacC mutant revealed a predominance of intron retention events, mainly involving introns 1 and 2, indicating defective splicing and potential nonsense-mediated decay of genes related to ion transport, metabolism, and genome maintenance. These alterations compromised energy balance, ergosterol biosynthesis, and cellular homeostasis. PacC-dependent AS generated alternative isoforms of cytoskeletal and metabolic proteins, including myosin-1 and a GH3 β-glucosidase, potentially modulating enzymatic activity, metabolic burden, and cell wall remodeling during infection. Exon-skipping in the chromatin remodeler RSC1 suggests PacC involvement in epigenetic regulation under host-mimicking conditions. Transmission electron microscopy revealed possible Woronin bodies, cytoplasmic disruption, and cell wall thinning in the mutant. Overall, PacC integrates transcriptional and post-transcriptional regulation to promote adaptation, survival, and virulence, highlighting AS as a regulatory layer linking environmental sensing to metabolic and epigenetic plasticity in pathogenic fungi.