Collaborative Research: Telomerase Structure and Evolution in Photosynthetic Eukaryotes

端粒酶是一种蛋白质和核糖核酸(RNA)的复合体，其功能是一种生物催化剂，通常称为酶。它对动物、植物和单细胞真核生物(如藻类)的忠实遗传至关重要。端粒酶复合体的大小、组成和细胞制造在不同的真核分类群中差异很大。这种变异使端粒酶成为研究酶的进化的优秀模型系统，酶是由蛋白质和RNA组成的复合体。2019年，这两个PI鉴定了植物端粒酶的RNA成分，使人们有可能对这一关键酶在动植物以外的真核生物群体中的进化提出新的问题。这项合作计划旨在探索单细胞真核生物端粒酶的组成和结构，这些真核生物具有光合作用，但与植物属于不同的分类类群。拟议的工作还包括为研究生和博士后研究员举办关于科学领导和谈判的研讨会，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的科学发现，并为科学和教育界提供一个关于各种端粒酶的经过精心策划的免费数据库。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的高度不同结构带来的知识缺口，尽管它们具有保守的基本功能。通过揭示光合作用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，动物和植物端粒酶的RNA组分的转录是不同的；植物端粒酶RNA是由RNAPol III转录的，而动物的端粒酶RNA是由RNAPol II转录的，需要Dyskerin蛋白。这项拟议的研究将调查一个意想不到的观察结果，即Dyskerin也是植物端粒酶RNA转录所必需的，尽管它是由不同的转录纳米机器催化的。将对端粒酶结构和功能的分析从陆地植物扩展到基端分枝的光合作用真核生物，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。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.