DSRNAS OF CRYPTOSPORIDIUM PARVUM

小隐孢子虫的 DSRNA

• 批准号: 6170902
• 负责人: Steve J Upton
• 金额: $ 16.53万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-15 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6170902
• 关键词: Cryptosporidium; antisense nucleic acid; chemical structure function; developmental genetics; double stranded RNA; gene expression; immunoelectron microscopy; life cycle; nucleic acid structure; protein kinase

DESCRIPTION (Adapted from the Applicant's Abstract): Cryptosporidium parvum is a gastrointestinal parasite capable of causing moderate to severe diarrheal disease in both humans and animals. The parasite is ubiquitous and is known to infect at least 79 different species of animals originating from more than 50 countries. Recent studies have demonstrated the presence of two high copy number, linear, double- stranded RNAs (dsRNAs) within sporozoites of 6 tested isolates of C. parvum, but not in 6 other species of the genus. Each of the DsRNAs has been purified and a library of cDNA clones representing both segments synthesized. Analysis of sequences has revealed the large segment (1786 nt) may encode and RNA-dependent RNA polymerase (RDRP), and the small segment (1374 nt) a putative protein kinase with limited similarity to mitogen-activated JNK protein kinase. No capsid protein has yet been found that co-purifies with the segments. The dsRNAs are extrachromosomal genetic element as they have no copies in the C. parvum genome, and the RDRP has an unusually high optimum temperature in vitro (50 degrees C). Investigators at Kansas State University propose to study the structure and function of the dsRNAs in C. parvum, as well as the putative proteins encoded by the dsRNA genes. Should these viral- like RNAs be found to encode proteins that modulate the parasite life- cycle, or be shown to affect the ability of the parasite to survive or induce pathogenicity, then they may also be found to represent useful therapeutic targets.

描述（改编自申请人的摘要）：隐孢子虫 Parvum是一种胃肠道寄生虫，能够导致中度 人类和动物的严重腹泻病。 寄生虫是 无处不在，已知至少感染79种不同的物种 来自50多个国家的动物。 最近的研究 证明存在两个高拷贝数，线性，双拷贝 滞留的RNA（DSRNA）在6个测试分离株的孢子岩中 parvum，但不在其他6种属中。 每个DSRNA都有 被纯化和代表这两个段的cDNA克隆库 合成。 序列的分析揭示了大段（1786 nt）可能编码和依赖RNA的RNA聚合酶（RDRP），而小 段（1374 NT）一种推定的蛋白激酶，与 有丝分裂原激活的JNK蛋白激酶。 尚无capsid蛋白 发现这是与各个细分市场的共同点。 DSRNA是 外染色体遗传元素，因为它们在孢子虫中没有副本 基因组，RDRP在体外具有异常高的最佳温度 （50度C）。 堪萨斯州立大学的调查人员建议 研究DSRNA在C. parvum中的结构和功能，以及 由DSRNA基因编码的推定蛋白。 这些病毒应该应该 像RNA一样，可以编码调节寄生虫寿命的蛋白质 - 循环，或被证明会影响寄生虫生存的能力或 诱导致病性，然后也可能发现它们代表有用 治疗靶标。