Integrated proteostasis and cell signaling circuits for the control of the stress response in fungi

Abstract

The regulation of gene expression in eukaryotes is knowingly responsive to varied stimuli through a network of competing and interwoven cell signaling pathways. This constitutes a central system associated with transistor functions in fungi, adaptively tuning physiological responses to environmental conditions. Such molecular circuits broadly combine the function of integral membrane receptors for the detection of changes outside the cell environment with a signaling cascade of phosphorylating protein kynases. Chaperone components like Hsp70 and Hsp90 ensure the correct turnover and proteostasis of these systems, which culminate in the recruitment of direct regulators of gene expression such as transcription factors (TF). However, alternative backup mechanisms play an important post-transcriptional role in shaping the fungal cell proteome. The full extent of this downstream regulation is yet to be investigated.Alternative splicing (AS) of pre-mRNA transcripts largely contributes to the diversity observed in the proteome of eukaryotic cells. Using a metatranscriptomic approach, we will compare RNA-Seq data with different views of the biology of the model species Trichophyton rubrum to investigate the role of alternative splicing in the stress response. Furthermore, we will invest in global analysis of the transcriptome in order to establish a relationship between pH-Pi and proteostasis networks in dermatophytes, also considering possible crosstalks with other relevant processes. The aim is to reveal regulatory circuits involved in environmental sensing processes and in the pathogenicity of fungi. (AU)