The StuA Transcription Factor and Alternative Splicing Mechanisms Drive the Levels of MAPK Hog1 Transcripts in the Dermatophyte Trichophyton rubrum

Author(s)

Martins-Santana, Leonardo ; Petrucelli, Monise Fazolin ; Sanches, Pablo R. ; Almeida, Fausto ; Martinez-Rossi, Nilce M. ; Rossi, Antonio

• Document type: Journal article
• Source: Mycopathologia; v. 189, n. 3, p. 14-pg., 2024-06-01.

Abstract

Trichophyton rubrum is a human fungal pathogen that causes dermatophytosis, an infection that affects keratinized tissues. Integrated molecular signals coordinate mechanisms that control pathogenicity. Transcriptional regulation is a core regulation of relevant fungal processes. Previous RNA sequencing data revealed that the absence of the transcription factor StuA resulted in the differential expression of the MAPK-related high glycerol osmolarity gene (hog1) in T. rubrum. Here we validated the role of StuA in regulating the transcript levels of hog1. We showed through RT-qPCR that transcriptional regulation controls hog1 levels in response to glucose, keratin, and co-culture with human keratinocytes. In addition, we also detected hog1 pre-mRNA transcripts that underwent alternative splicing, presenting intron retention in a StuA-dependent mechanism. Our findings suggest that StuA and alternative splicing simultaneously, but not dependently, coordinate hog1 transcript levels in T. rubrum. As a means of preventing and treating dermatophytosis, our results contribute to the search for new potential drug therapies based on the molecular aspects of signaling pathways in T. rubrum. (AU)

• FAPESP's process: 19/22596-9 - Molecular mechanisms associated with pathogenicity and resistance in fungi: strategies for treating dermatophytosis
• Grantee: Nilce Maria Martinez-Rossi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/10255-2 - Transcription factors and cell signaling pathways in pathogenicity and modulation of immune response
• Grantee: Leonardo Martins Santana
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/10359-2 - Comparative systematic analysis of transcriptomes in the elucidation of potential antifungal targets
• Grantee: Monise Fazolin Petrucelli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral