Gardner M J, Williamson D H, Wilson R J
Division of Parasitology, National Institute for Medical Research, Mill Hill, London, U.K.
Mol Biochem Parasitol. 1991 Jan;44(1):115-23. doi: 10.1016/0166-6851(91)90227-w.
A 3.5-kb Sau3AI fragment was cloned from a circular DNA molecule isolated from the human malaria parasite Plasmodium falciparum and found to contain two contiguous open reading frames. These encode portions of beta and beta' subunits of an RNA polymerase similar to prokaryotic and chloroplast RNA polymerases, and contain highly conserved structural elements. The Plasmodium genes are arranged in a polycistronic transcription unit, as in both Escherichia coli and chloroplast genomes, and are transcribed in erythrocytic stages. These results suggest that the circular DNA may be an unusual mitochondrial DNA, or derived from an unidentified organelle. Because the beta subunit of prokaryotic RNA polymerases is the specific target of the antibiotic rifampicin, our observations may explain the high sensitivity of P. falciparum to this drug in vitro and indicate a new target for chemotherapy.
从人类疟原虫恶性疟原虫分离出的一个环状DNA分子中克隆出一个3.5千碱基的Sau3AI片段,发现它含有两个相邻的开放阅读框。这些开放阅读框编码一种与原核生物和叶绿体RNA聚合酶相似的RNA聚合酶的β和β'亚基的部分,并含有高度保守的结构元件。疟原虫基因像在大肠杆菌和叶绿体基因组中一样,排列在一个多顺反子转录单元中,并在红细胞阶段进行转录。这些结果表明,该环状DNA可能是一种不寻常的线粒体DNA,或者源自一个未鉴定的细胞器。由于原核生物RNA聚合酶的β亚基是抗生素利福平的特异性靶点,我们的观察结果可能解释了恶性疟原虫在体外对这种药物的高敏感性,并指出了一个新的化疗靶点。