RNA triphosphatase is essential in Schizosaccharomyces pombe and Candida albicans
Open Access
- 20 November 2001
- journal article
- Published by Institute of Electrical and Electronics Engineers (IEEE)
- Vol. 1, 29
- https://doi.org/10.1186/1471-2180-1-29
Abstract
The first two steps in the capping of cellular mRNAs are catalyzed by the enzymes RNA triphosphatase and RNA guanylyltransferase. Although structural and mechanistic differences between fungal and mammalian RNA triphosphatases recommend this enzyme as a potential antifungal target, it has not been determined if RNA triphosphatase is essential for the growth of fungal species that cause human disease. We show by classical genetic methods that the triphosphatase (Pct1) and guanylyltransferase (Pce1) components of the capping apparatus in the fission yeast Schizosaccharomyces pombe are essential for growth. We were unable to disrupt both alleles of the Candida albicans RNA triphosphatase gene CaCET1, implying that the RNA triphosphatase enzyme is also essential for growth of C. albicans, a human fungal pathogen. Our results provide the first genetic evidence that cap synthesis is essential for growth of an organism other than Saccharomyces cerevisiae and they validate RNA triphosphatase as a target for antifungal drug discovery.This publication has 25 references indexed in Scilit:
- An Essential Function of Saccharomyces cerevisiae RNA Triphosphatase Cet1 Is to Stabilize RNA Guanylyltransferase Ceg1 against Thermal InactivationJournal of Biological Chemistry, 2001
- Structure-Function Analysis of the Active Site Tunnel of Yeast RNA TriphosphataseJournal of Biological Chemistry, 2001
- RNA Triphosphatase Component of the mRNA Capping Apparatus of Paramecium bursaria Chlorella Virus 1Journal of Virology, 2001
- Characterization of the mRNA Capping Apparatus of Candida albicansJournal of Biological Chemistry, 2001
- Structure and Mechanism of Yeast RNA TriphosphataseCell, 1999
- Yeast and Viral RNA 5′ Triphosphatases Comprise a New Nucleoside Triphosphatase FamilyJournal of Biological Chemistry, 1998
- Isolation and characterization of the Candida albicans gene for mRNA 5′‐triphosphatase: association of mRNA 5′‐triphosphatase and mRNA 5′‐guanylyltransferase activities is essential for the function of mRNA 5′‐capping enzyme in vivo1FEBS Letters, 1998
- Isolation and Characterization of the Yeast mRNA Capping Enzyme β Subunit Gene Encoding RNA 5′-Triphosphatase, Which Is Essential for Cell ViabilityBiochemical and Biophysical Research Communications, 1997
- Covalent catalysis in nucleotidyl transfer reactions: essential motifs in Saccharomyces cerevisiae RNA capping enzyme are conserved in Schizosaccharomyces pombe and viral capping enzymes and among polynucleotide ligases.Proceedings of the National Academy of Sciences, 1994
- Improved method for high efficiency transformation of intact yeast cellsNucleic Acids Research, 1992