DSRNAS OF CRYPTOSPORIDIUM PARVUM

小隐孢子虫的 DSRNA

• 批准号: 2712352
• 负责人: Steve J Upton
• 金额: $ 15.99万
• 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 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2712352
• 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，能够引起中度至 人类和动物的严重腹泻病。 寄生虫是 无处不在，已知可感染至少 79 种不同物种 来自50多个国家的动物。 最近的研究有 证明存在两个高拷贝数、线性、双拷贝 6 个测试的 C. 菌株子孢子内的链 RNA (dsRNA) parvum，但不在该属的其他 6 个物种中。 每个 DsRNA 都有 已纯化并代表两个片段的 cDNA 克隆文库 合成的。 序列分析揭示了大片段（1786 nt）可能编码RNA依赖性RNA聚合酶（RDRP），并且小 片段 (1374 nt) 与有限相似性的推定蛋白激酶 有丝分裂原激活的 JNK 蛋白激酶。 目前尚未发现衣壳蛋白 发现与片段共同纯化。 dsRNA 是 染色体外遗传元件，因为它们在 C. parvum 中没有副本 基因组，并且 RDRP 在体外具有异常高的最适温度 （50 摄氏度）。 堪萨斯州立大学的研究人员提议 研究 C. parvum 中 dsRNA 的结构和功能，以及 由 dsRNA 基因编码的推定蛋白质。 如果这些病毒—— 像RNA一样被发现可以编码调节寄生虫生命的蛋白质—— 周期，或被证明会影响寄生虫的生存能力或 诱导致病性，那么它们也可能被发现代表有用的 治疗目标。