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) 的复合物，具有生物催化剂的作用，通常称为酶。 它对于动物、植物和藻类等单细胞真核生物的忠实遗传遗传至关重要。端粒酶复合物的大小、组成和细胞制造在不同的真核分类群中存在显着差异。 这种变异使端粒酶成为研究由蛋白质和 RNA 组成的复合物的酶的进化的杰出模型系统。 2019 年，两位 PI 鉴定了植物端粒酶的 RNA 成分，使得人们有可能对这种关键酶在动植物之外的真核群体中的进化提出新的问题。 该合作提案旨在探索单细胞真核生物端粒酶的成分和结构，这些单细胞真核生物具有光合作用，但与植物属于不同的分类群。 拟议的工作还包括为研究生和博士后研究员举办有关科学领导力和谈判的研讨会，为不同的本科生提供研究机会，以了解进化生物学、结构生物学和遗传学方面的科学发现，并为科学和教育界提供精心策划的免费机会关于各种端粒酶的数据库。 更具体地说，这项研究解决了纤毛虫、植物和脊椎动物端粒酶结构高度差异所带来的知识差距，尽管它们的基本功能是保守的。 通过揭示光合生物端粒酶的组成和结构，可能会发现新的辅助因子和 RNA-蛋白质相互作用的新模式。此外，端粒酶RNA成分的转录在动物和植物中是不同的；植物端粒酶RNA由RNA Pol III转录，而动物端粒酶RNA由RNA Pol II转录，并且需要蛋白质dyskerin。拟议的研究将调查一个意想不到的观察结果，即植物端粒酶 RNA 的转录也需要 Dykerin，尽管它是由不同的转录纳米机器催化的。 将端粒酶结构和功能的分析扩展到陆地植物之外的基础分支光合真核生物，为揭示第一个端粒酶的祖先特征提供了独特的机会。 更广泛地说，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转变的基本规则。该奖项反映了 NSF 的法定使命，并被认为值得支持通过使用基金会的智力优点和更广泛的影响审查标准进行评估。