Pei Y, Schwer B, Saiz J, Fisher R P, Shuman S
Molecular Biology and Cell Biology Programs, Sloan-Kettering Institute, New York, NY 10021, USA.
BMC Microbiol. 2001;1:29. doi: 10.1186/1471-2180-1-29. Epub 2001 Nov 20.
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.
细胞信使核糖核酸（mRNA）加帽过程的前两步由RNA三磷酸酶和RNA鸟苷酸转移酶催化。尽管真菌和哺乳动物RNA三磷酸酶在结构和机制上存在差异，使得该酶成为潜在的抗真菌靶点，但尚未确定RNA三磷酸酶对于引起人类疾病的真菌物种的生长是否必不可少。
我们通过经典遗传学方法表明，裂殖酵母粟酒裂殖酵母中加帽装置的三磷酸酶（Pct1）和鸟苷酸转移酶（Pce1）成分对生长至关重要。我们无法破坏白色念珠菌RNA三磷酸酶基因CaCET1的两个等位基因，这意味着RNA三磷酸酶对人类真菌病原体白色念珠菌的生长也必不可少。
我们的结果提供了首个遗传学证据，表明帽合成对于酿酒酵母以外的生物体的生长至关重要，并且验证了RNA三磷酸酶作为抗真菌药物发现的靶点。
