An investigation into eukaryotic pseudouridine synthases

J Bioinform Comput Biol. 2014 Aug;12(4):1450015. doi: 10.1142/S0219720014500152. Epub 2014 Aug 1.

Abstract

A common post-transcriptional modification of RNA is the conversion of uridine to its isomer pseudouridine. We investigated the biological significance of eukaryotic pseudouridine synthases using the yeast Saccharomyces cerevisiae. We conducted a comprehensive statistical analysis on growth data from automated perturbation (gene deletion) experiments, and used bi-logistic curve analysis to characterise the yeast phenotypes. The deletant strains displayed different alteration in growth properties, including in some cases enhanced growth and/or biphasic growth curves not seen in wild-type strains under matched conditions. These results demonstrate that disrupting pseudouridine synthases can have a significant qualitative effect on growth. We further investigated the significance of post-transcriptional pseudouridine modification through investigation of the scientific literature. We found that (1) In Toxoplasma gondii, a pseudouridine synthase gene is critical in cellular differentiation between the two asexual forms: Tachyzoites and bradyzoites; (2) Mutation of pseudouridine synthase genes has also been implicated in human diseases (mitochondrial myopathy and sideroblastic anemia (MLASA); dyskeratosis congenita). Taken together, these results are consistent with pseudouridine synthases having a Gene Ontology function of "biological regulation".

Keywords: RNA; Saccharomyces cerevisiae; biological regulation; growth analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sideroblastic / genetics
  • Eukaryotic Cells
  • Gene Deletion
  • Humans
  • Hydro-Lyases / genetics
  • Intramolecular Transferases / genetics*
  • Intramolecular Transferases / metabolism*
  • Multigene Family
  • Mutation
  • Pseudouridine / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Toxoplasma / physiology*

Substances

  • Pus7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Pseudouridine
  • Hydro-Lyases
  • pseudouridylate synthetase
  • Intramolecular Transferases
  • pseudouridine synthases