Pseudouridine synthase 7 impacts Candida albicans rRNA processing and morphological plasticity.

Area of Science:

• Molecular Biology
• Mycology
• Biochemistry

Background:

• RNA modifications are essential for cellular function, with pseudouridylation being a prevalent type catalyzed by pseudouridine synthases.
• Pseudouridine synthase 7 (Pus7) in Saccharomyces cerevisiae modifies various RNA types, but its homologues in other yeasts, like Candida albicans, have uncharacterized substrates and functions.

Purpose of the Study:

• To investigate the function of Candida albicans PUS7 (CaPUS7) and identify its RNA substrates.
• To determine the role of CaPus7 in fungal physiology, antifungal drug sensitivity, and virulence.

Main Methods:

• CRISPR-mediated genome editing was employed to create a PUS7 deletion mutant in Candida albicans.
• Analysis included assessment of rRNA processing, cell surface hydrophobicity, temperature sensitivity, filamentation, drug sensitivity, and virulence in a Galleria mellonella (wax moth) model.

Main Results:

• Absence of CaPUS7 resulted in significant defects in rRNA processing and reduced cell surface hydrophobicity.
• CaPUS7 deletion led to temperature sensitivity, impaired filamentation, altered antifungal drug susceptibility, and decreased virulence in the wax moth model.
• CaPus7 was found to modify tRNA residues in C. albicans, but not all substrates modified by S. cerevisiae Pus7.

Conclusions:

• Candida albicans Pus7 plays a vital role in maintaining fungal vigor, influencing multiple cellular processes.
• CaPus7 exhibits distinct substrate specificity and biological functions compared to its Saccharomyces cerevisiae homologue, suggesting specialized roles in pathogenic fungi.