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.

National Science Foundation (NSF)
Division of Molecular and Cellular Biosciences (MCB)
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Candi Phoebe Lostroh
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Arizona State University
United States
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