RNA Processing in Trypanosome Mitochondria

锥虫线粒体中的 RNA 加工

• 批准号: 1122109
• 负责人: Jorge Cruz-Reyes
• 金额: $ 61.5万
• 依托单位: Texas A&M Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1122109&HistoricalAwards=false
• 关键词: RNA; Processing; Trypanosome; Mitochondria

Intellectual merit: Trypanosomes are kinetoplastid protozoa that contain a unique mitochondrial genome known as the kinetoplast (kDNA). When genes within the kDNA are expressed, the corresponding messenger RNAs that are synthesized are extensively edited in reactions directed by hundreds of small guide RNAs (gRNAs). This project concerns the maturation of these gRNAs. Precursor RNA molecules are synthesized that include multiple gRNAs, and these precursors are processed by unknown mechanisms and enzymes that precede editing. This research characterizes a novel enzyme termed mRPN1 (mitochondrial RNA precursor-processing endonuclease 1), which is required for efficient gRNA biogenesis in Trypanosoma brucei. mRPN1 cleaves double-stranded RNA with a specificity that is reminiscent of bacterial RNase III and eukaryotic Dicer, and it forms a complex with three protein subunits, which is thought to facilitate entry of gRNA into the RNA editing pathway. The role of mRPN1 and its associated subunits in the mRPN1 complex will be investigated. Since gRNA biogenesis is virtually an unexplored field in trypanosome RNA biology, these studies should open new questions and potentially new paradigms in early divergent kinetoplastids. Broader impacts: This research involves a strong team of collaborators at Texas A&M and other institutions, and its educational component directly impacts a graduate student, who is an ethnic minority, a postdoctoral fellow, and an undergraduate student. The findings will be communicated to the scientific community through the publication of data in prominent research journals, and at local and international meetings. The discovery of mRPN1 and its involvement in gRNA biogenesis was reported in the spring 2011 at both the Gordon Research Conference on RNA editing and the Kinetoplastid Molecular Cell Biology Meeting.

智力优点：锥虫是动质体原生动物，含有一个独特的线粒体基因组，称为动质体（kDNA）。当kDNA中的基因表达时，合成的相应信使RNA在由数百个小向导RNA（gRNA）指导的反应中被广泛编辑。该项目涉及这些gRNA的成熟。合成的前体RNA分子包括多个gRNA，并且这些前体由编辑之前的未知机制和酶加工。这项研究表征了一种名为mRPN 1（线粒体RNA酶处理内切核酸酶1）的新型酶，该酶是布氏锥虫中有效gRNA生物合成所必需的。 mRPN1以一种让人联想到细菌RNase III和真核生物Dicer的特异性切割双链RNA，并且它与三个蛋白质亚基形成复合物，这被认为有助于gRNA进入RNA编辑途径。 将研究mRPN1及其相关亚基在mRPN1复合物中的作用。 由于gRNA的生物发生实际上是锥虫RNA生物学中一个未探索的领域，这些研究应该在早期趋异动质体中开辟新的问题和潜在的新范式。 更广泛的影响：这项研究涉及德克萨斯州A M和其他机构的强大合作者团队，其教育部分直接影响研究生，他是少数民族，博士后研究员和本科生。研究结果将通过在著名的研究期刊上发表数据以及在地方和国际会议上向科学界通报。2011年春天，在戈登RNA编辑研究会议和动质体分子细胞生物学会议上报告了mRPN 1的发现及其参与gRNA生物发生。