Pseudouridine synthase 7 impacts Candida albicans rRNA processing and morphological plasticity

Yeast. 2019 Nov;36(11):669-677. doi: 10.1002/yea.3436. Epub 2019 Aug 16.

Abstract

RNA can be modified in over 100 distinct ways, and these modifications are critical for function. Pseudouridine synthases catalyse pseudouridylation, one of the most prevalent RNA modifications. Pseudouridine synthase 7 modifies a variety of substrates in Saccharomyces cerevisiae including tRNA, rRNA, snRNA, and mRNA, but the substrates for other budding yeast Pus7 homologues are not known. We used CRISPR-mediated genome editing to disrupt Candida albicans PUS7 and find absence leads to defects in rRNA processing and a decrease in cell surface hydrophobicity. Furthermore, C. albicans Pus7 absence causes temperature sensitivity, defects in filamentation, altered sensitivity to antifungal drugs, and decreased virulence in a wax moth model. In addition, we find C. albicans Pus7 modifies tRNA residues, but does not modify a number of other S. cerevisiae Pus7 substrates. Our data suggests C. albicans Pus7 is important for fungal vigour and may play distinct biological roles than those ascribed to S. cerevisiae Pus7.

Keywords: C. albicans; Pus7; RNA modification; pseudouridine; pseudouridine synthase 7; pseudouridylation; rRNA processing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • CRISPR-Cas Systems
  • Candida albicans / drug effects
  • Candida albicans / enzymology
  • Candida albicans / genetics*
  • Candidiasis / microbiology
  • Gene Deletion
  • Gene Editing
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Intramolecular Transferases / genetics
  • Intramolecular Transferases / metabolism*
  • Larva / microbiology
  • Moths / microbiology
  • RNA Processing, Post-Transcriptional
  • RNA, Fungal / genetics*
  • RNA, Ribosomal / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Substrate Specificity

Substances

  • Antifungal Agents
  • Pus7 protein, S cerevisiae
  • RNA, Fungal
  • RNA, Ribosomal
  • Saccharomyces cerevisiae Proteins
  • Intramolecular Transferases
  • pseudouridine synthases