Collaborative Research: Telomerase Structure and Evolution in Photosynthetic Eukaryotes

合作研究：光合真核生物的端粒酶结构和进化

• 批准号: 2047915
• 负责人: Dorothy Shippen
• 金额: $ 75万
• 依托单位: Texas A&M AgriLife Research
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2047915&HistoricalAwards=false
• 关键词: Collaborative; Research; Telomerase; Structure; Evolution

Telomerase is a complex of proteins and ribonucleic acid (RNA) that functions as a biological catalyst known in general as an enzyme. It is essential for faithful genetic inheritance in animals, plants, and single-celled eukaryotes such as algae. The size, composition and cellular manufacture of the telomerase complex varies dramatically across diverse eukaryotic taxonomic groups. This variation makes telomerase an outstanding model system for examining the evolution of enzymes that are complexes comprised of both protein and RNA. In 2019, the two PIs identified the RNA component of plant telomerase, making it possible to ask new questions about the evolution of this critical enzyme in eukaryotic groups in addition to animals and plants. The collaborative proposal intends to explore the components and structure of telomerases from single-celled eukaryotes that are photosynthetic but belong to different taxonomic groups than plants. The proposed work also includes workshops on scientific leadership and negotiation for graduate students and post-doctoral fellows, provides research opportunities for diverse undergraduates to learn about scientific discovery in evolutionary biology, structural biology and genetics, and provides scientific and educational communities with a curated free database about diverse telomerase enzymes. More specifically, this research addresses a knowledge gap presented by the highly divergent structures of ciliate, plant, and vertebrate telomerase enzymes despite their conserved essential function. By revealing the composition and architecture of telomerase from photosynthetic organisms, novel accessory factors and new modes of RNA-protein interaction may be uncovered. In addition, the transcription of the RNA component of telomerases is different in animals and plants; plant telomerase RNA is transcribed by RNA Pol III while in animals the telomerase RNA is transcribed by RNA Pol II and requires the protein dyskerin. The proposed research will investigate the unexpected observation that dyskerin is also needed for transcription of plant telomerase RNA even though it is catalyzed by different transcription nanomachines. Expanding analysis of telomerase structure and function beyond land plants to the basal-branching photosynthetic eukaryotes provides a unique opportunity to reveal the ancestral features of the first telomerase. More broadly, comprehensive analysis of telomerase structure, function and evolution will help to establish fundamental rules underlying the biomolecular transition from an RNA world to cellular life that primarily uses protein-based catalysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

端粒酶是蛋白质和核糖核酸（RNA）的复合体，该蛋白质（RNA）通常是一种被称为酶的生物催化剂。 这对于动物，植物和单细胞真核生物（例如藻类）中的忠实遗传遗传至关重要。端粒酶复合物的大小，组成和细胞制造在各种真核分类学组之间差异很大。 这种变化使端粒酶成为检查由蛋白质和RNA组成的复合物的演化的出色模型系统。 2019年，这两个PI确定了植物端粒酶的RNA成分，使得除了动物和植物外，还可以询问有关这种关键酶在真核基团中的进化的新问题。 该协作提案旨在探索来自光合作用但属于植物不同的分类群的单细胞真核生物的端粒成分和结构。 拟议的工作还包括有关研究生和博士后研究员的科学领导力和谈判的研讨会，为多样化的本科生提供了研究机会，以了解进化生物学，结构生物学和遗传学中的科学发现，并为科学和教育社区提供有关多元化型望远镜Enzemess的策划自由数据库的科学和教育社区。 更具体地说，这项研究探讨了纤毛，植物和脊椎动物端粒酶酶的高度分歧结构所带来的知识差距，尽管它们是保守的基本功能。 通过揭示来自光合生物体的端粒酶的组成和结构，可以发现新的附件因子和新的RNA-蛋白质相互作用模式。另外，动物和植物中端粒酶的RNA成分的转录不同。植物端粒酶RNA由RNA POL III转录，而在动物中，端粒酶RNA由RNA POL II转录，需要蛋白质异常。拟议的研究将调查意外的观察结果，即植物端粒酶RNA也需要dyskerin，即使它被不同的转录纳米机催化。 扩大对土地植物以外的端粒酶结构和功能的分析到基底分支光合真核生物，这为揭示了第一个端粒酶的祖先特征提供了独特的机会。 更广泛的，对端粒酶结构，功能和进化的全面分析将有助于建立从RNA世界到主要使用基于蛋白质的催化的细胞生命的生物分子过渡为基础的基本规则。这项奖项反映了NSF的法定任务，并通过使用该基金会的知识优点和广泛影响来评估NSF的法定任务，并通过评估有价值。