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Alternative splicing is a driving force that tunes metabolic adaptations to virulence traits in the dermatophyte Trichophyton rubrum
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Alternative splicing is a driving force that tunes metabolic adaptations to virulence traits in the dermatophyte Trichophyton rubrum
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Journal Article
Alternative splicing is a driving force that tunes metabolic adaptations to virulence traits in the dermatophyte Trichophyton rubrum
2025
Overview
Alternative splicing (AS), a common process in pathogenic fungal species, is not fully understood. We hypothesized that AS is a critical regulatory mechanism that enables species to undergo continuous adaptations during interactions with challenging host environments.
We utilized the model species
to contextualize the role of AS in fungal physiology and virulence. We performed transcriptome-wide splicing analysis to search for AS events in RNA-sequencing data of
grown in keratin. This scenario mimicked infection
and allowed us to map biologically relevant splicing events.
Overall, the results showed that AS is recruited to regulate approximately 12.6% of the
genome under an infection-like scenario. We extended this analysis to
infection models of
grown on human nails and cocultured them with human HaCaT keratinocytes. We found that AS affects a wide range of cellular processes, including amino acid and carbohydrate metabolism, cell signaling, protein folding and transport, transcription, and translation. We showed that transcription factors such as PacC and Ap1 govern the major features of fungal virulence and metabolism and are controlled by the spliceosome machinery under different infection-like conditions.
Our data indicate that mRNA isoforms originating from AS contribute to the adaptation of
, demonstrating that AS of transcription factor genes plays a central role in fungal pathogenesis. The transcription and splicing machinery tune fungal physiology to achieve an optimal metabolic balance in virulence traits during infection.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Adaptation, Physiological - genetics
/ Arthrodermataceae - genetics
/ Arthrodermataceae - metabolism
/ Arthrodermataceae - pathogenicity
/ Fungal Proteins - metabolism
/ Fungi
/ Gene Expression Regulation, Fungal
/ Glucose
/ Humans
/ Isoforms
/ Keratin
/ Keratinocytes - microbiology
/ Nitrogen
/ PacC
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
