Abstract
Pathogenic fungi hide from their hosts by camouflage, obscuring immunogenic cell wall components such as beta-glucan with innocuous coverings such as mannoproteins and alpha-glucan that are less readily recognised by the host. Attempts to understand how such processes are regulated have met with varying success. Typically studies focus on understanding the transcriptional response of fungi to either their reservoir environment or the host. However, such approaches do not fully address this research question, due to the layers of post-transcriptional and post-translational regulation that occur within a cell. Although in animals the impact of post-transcriptional and post-translational regulation has been well characterised, our knowledge of these processes in the fungal kingdom is more limited. Mutations in RNA-binding proteins, like Ssd1 and Candida albicans Slr1, affect cell wall composition and fungal virulence indicating that post-transcriptional regulation plays a key role in these processes. Here, we review the current state of knowledge of fungal post-transcriptional regulation, and link this to potential mechanisms of immune evasion by drawing on studies from model yeast and plant pathogenic fungi. We highlight several RNA-binding proteins that regulate cell wall synthesis and could be involved in local translation of cell wall components. Expanding our knowledge on post-transcriptional regulation in human fungal pathogens is essential to fully comprehend fungal virulence strategies and for the design of novel antifungal therapies.
Highlights
The fungal cell wall is a dynamic multi-layered organelle composed of polysaccharides and proteins
The composition of the cell wall varies from species to species, but overall the cell wall consists of an inner skeletal layer of chitin and beta-glucan that forms the exoskeleton of the cell, maintaining cell shape, rigidity and turgor pressure, while the outer layer of the cell wall is formed of glycosylated mannoproteins, that provide specific cell functions like adhesion and invasion
Given that cell wall remodelling is required for fungal morphogenesis, deletion of RNA binding proteins involved in the regulation of cell wall biosynthesis results in morphological defects, attenuating virulence
Summary
The fungal cell wall is a dynamic multi-layered organelle composed of polysaccharides and proteins. From the 42 RBPs studied, seven were shown to bind mRNAs enriched in cell wall synthesis (Ssd1, Scp160, Pub1, Mpt5, Mrn1, Khd1 and Bfr1), highlighting the importance of posttranscriptional regulation in S. cerevisiae cell wall biogenesis (Fig. 3). The precise Ssd1 binding sites have been identified in S. cerevisiae, and are located mostly near the start codons of mRNAs that encode a subset of cell wall proteins (Bayne et al 2021).
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