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

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 respons...

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Autores principales: Neves-da-Rocha, João, Bitencourt, Tamires A., de Oliveira, Vanderci M., Sanches, Pablo R., Rossi, Antonio, Martinez-Rossi, Nilce M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830096/
https://www.ncbi.nlm.nih.gov/pubmed/31590387
http://dx.doi.org/10.3390/cells8101206
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author Neves-da-Rocha, João
Bitencourt, Tamires A.
de Oliveira, Vanderci M.
Sanches, Pablo R.
Rossi, Antonio
Martinez-Rossi, Nilce M.
author_facet Neves-da-Rocha, João
Bitencourt, Tamires A.
de Oliveira, Vanderci M.
Sanches, Pablo R.
Rossi, Antonio
Martinez-Rossi, Nilce M.
author_sort Neves-da-Rocha, João
collection PubMed
description 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 °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.
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spelling pubmed-68300962019-11-18 Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum Neves-da-Rocha, João Bitencourt, Tamires A. de Oliveira, Vanderci M. Sanches, Pablo R. Rossi, Antonio Martinez-Rossi, Nilce M. Cells Article 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 °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. MDPI 2019-10-05 /pmc/articles/PMC6830096/ /pubmed/31590387 http://dx.doi.org/10.3390/cells8101206 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Neves-da-Rocha, João
Bitencourt, Tamires A.
de Oliveira, Vanderci M.
Sanches, Pablo R.
Rossi, Antonio
Martinez-Rossi, Nilce M.
Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum
title Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum
title_full Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum
title_fullStr Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum
title_full_unstemmed Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum
title_short Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in Trichophyton rubrum
title_sort alternative splicing in heat shock protein transcripts as a mechanism of cell adaptation in trichophyton rubrum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830096/
https://www.ncbi.nlm.nih.gov/pubmed/31590387
http://dx.doi.org/10.3390/cells8101206
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