Department of Genetics, Ribeirão Preto Medical Schoool, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Department of Biochemistry and Immunology, Ribeirão Preto Medical Schoool, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Mycopathologia. 2024 May 5;189(3):37. doi: 10.1007/s11046-024-00842-5.
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.
红色毛癣菌是一种人类真菌病原体,可引起皮肤癣菌病,即感染角蛋白组织的疾病。整合的分子信号协调控制致病性的机制。转录调控是相关真菌过程的核心调控。先前的 RNA 测序数据表明,转录因子 StuA 的缺失导致红色毛癣菌中与 MAPK 相关的高甘油渗透压基因(hog1)的差异表达。在这里,我们验证了 StuA 在调节 hog1 转录水平中的作用。我们通过 RT-qPCR 表明,转录调控控制葡萄糖、角蛋白和与人角质形成细胞共培养时 hog1 的水平。此外,我们还检测到 hog1 前体 mRNA 转录本发生了选择性剪接,在 StuA 依赖的机制中存在内含子保留。我们的研究结果表明,StuA 和选择性剪接同时但不是独立地协调红色毛癣菌中 hog1 转录本的水平。作为预防和治疗皮肤癣菌病的一种手段,我们的研究结果为基于红色毛癣菌信号通路的分子方面寻找新的潜在药物治疗方法做出了贡献。