Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum

Author(s)

Neves-da-Rocha, Joao ^[1] ; Bitencourt, Tamires A. ^[1] ; de Oliveira, Vanderci M. ^[1] ; Sanches, Pablo R. ^[1] ; Rossi, Antonio ^[1] ; Martinez-Rossi, Nilce M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: CELLS; v. 8, n. 10 OCT 2019.
• Web of Science Citations: 0

Abstract

Heat shock proteins (HSPs) are involved in critical processes like host tissue invasion, resistance, and pathogenicity in dermatophytes. RNA-Seq analysis of Trichophyton rubrum exposed to undecanoic acid (UDA) revealed intron retention events in HSP transcripts. Because HSPs are modulated in response to various stimuli and as alternative splicing (AS) can result in a broad diversity in the proteome of eukaryotic cells, our objective was to confirm the aforementioned retention events, investigating their consequences and extent. Furthermore, we aimed to determine: (1) the expression profile of HSP genes in an infection-like scenario and (2) the importance of Hsp90 for the keratinolytic potential of T. rubrum. RT and qPCR analyses comparing the exposure to UDA and terbinafine (TRB) confirmed the presence of two mRNA isoforms of the hsp7-like gene, with distinct expression patterns in response to UDA and TRB. The HSP expression profile revealed two upregulated, three downregulated, and four unmodulated transcripts; Hsp90 inhibition by 17-AAG resulted in a significant decrease in keratinolytic potential at 37 degrees C. Altogether, these results broaden the current knowledge on the importance of HSP-mediated pathways for cell adaptation and other aspects of dermatophyte biology, indicating that HSP network proteins can be potential targets for antifungal therapy. (AU)

• FAPESP's process: 15/23435-8 - Molecular mechanisms involved in resistance and adaptive response to fungal inhibitors
• Grantee: Tamires Aparecida Bitencourt
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/03847-7 - Molecular characterization of mechanisms involved in pathogenicity and cell signaling in fungi
• Grantee: Nilce Maria Martinez-Rossi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/15458-6 - Alternative splicing in genes coding for HSPs as a response to antifungals in the dermatophyte Trichophyton rubrum
• Grantee: João Neves da Rocha Fonseca
• Support Opportunities: Scholarships in Brazil - Scientific Initiation