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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Mycopathologia; v. 189, n. 3, p. 14-pg., 2024-06-01.

Resumo

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)

• Processo FAPESP: 19/22596-9 - Mecanismos moleculares associados à patogenicidade e resistência em fungos: estratégias para o tratamento de dermatofitoses
• Beneficiário: Nilce Maria Martinez-Rossi
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 21/10255-2 - Fatores de transcrição e vias de sinalização celular na patogenicidade e modulação da resposta imune
• Beneficiário: Leonardo Martins Santana
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 21/10359-2 - Análise sistemática comparativa de transcriptomas na elucidação de potenciais alvos antifúngicos
• Beneficiário: Monise Fazolin Petrucelli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado