RNA triphosphatase is essential in Schizosaccharomyces pombe and Candida albicans.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Pei
Y
Y
Molecular Biology and Cell Biology Programs, Sloan-Kettering Institute, New York, NY 10021, USA. y-pei@ski.mskc.org
Schwer
B
B
Saiz
J
J
Fisher
R P
RP
Shuman
S
S
D017766:Acid Anhydride Hydrolases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002176:Candida albicans / Q000201:enzymology* / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D017353:Gene Deletion; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D009713:Nucleotidyltransferases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011487:Protein Conformation; D012315:RNA Caps / Q000378:metabolism / Q000502:physiology; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000502:physiology; D000098556:mRNA Guanylyltransferases
D012315:RNA Caps; D009713:Nucleotidyltransferases; D000098556:mRNA Guanylyltransferases; D017766:Acid Anhydride Hydrolases; C023090:RNA triphosphatase