Dataset Information

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

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 °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.

SUBMITTER: Neves-da-Rocha J

PROVIDER: S-EPMC6830096 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in <i>Trichophyton rubrum</i>.

Neves-da-Rocha João J Bitencourt Tamires A TA Oliveira Vanderci M de VM Sanches Pablo R PR Rossi Antonio A Martinez-Rossi Nilce M NM

Cells 20191005 10

Heat shock proteins (HSPs) are involved in critical processes like host tissue invasion, resistance, and pathogenicity in dermatophytes. RNA-Seq analysis of <i>Trichophyton rubrum</i> 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, inve ...[more]

PMID: 31590387

Similar Datasets

Project description:Trichophyton rubrum is the most common causative agent of dermatophytosis worldwide and uses keratinized substrates such as skin and nails as its main source of nutrition during infection. Its pathogenic character relies on colonization and viability maintenance at the target host sites. Since fungal physiology must adapt and respond to host conditions for the successful establishment of infection, biological mechanisms are constantly being triggered by T. rubrum to guarantee its survival in the host environment. The ability of this fungus to sense and modulate the secretion of specific proteases according to environmental pH signaling is considered as a pivotal virulence factor for effective invasion and persistence of infection in the host. Transcriptional regulation of genes encoding specific proteases, such as peptidases, is a key biological process that drives physiological modulation to meet fungal requirements. It accomplishes a robust balance among transcript isoforms that can be directed to perform distinct cellular functions. Thus, alternative splicing mechanisms are suitable for fungal cells to establish a balance toward reprogramming protein translation to impair or boost physiological conditions. In this study, we investigated the role of alternative splicing, especially intron retention events, in generating isoforms of virulence factors in T. rubrum mediated by transcriptional coordination of the protein StuA, a recently described transcription factor in this fungus. By analyzing the previous gene expression data provided by RNA-sequencing and after validation by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), we observed that two peptidase-coding genes (TERG_00734 and TERG_04614) could be direct targets of alternative splicing in the presence of keratin. Furthermore, protease isoforms generated by alternative splicing in T. rubrum were also detected in a co-culture with human keratinocytes, highlighting the role of these proteins in keratin deconstruction. Our results strongly suggest the influence of StuA on the regulation of virulence factors in T. rubrum and dermatophyte infections by triggering the transcription of the peptidase genes mentioned above in an alternative splicing-independent balance. The results elucidate how fungal cells drive alternate splicing to promote physiological adaptations and show that transcriptional regulation and virulence traits are robust elements required for dermatophyte infection.

Dataset Information

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

Publications

Alternative Splicing in Heat Shock Protein Transcripts as a Mechanism of Cell Adaptation in <i>Trichophyton rubrum</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets