Structural Biology of Telomerase and Interactions at Telomeres

Juli Feigon is Distinguished Professor in the Department of Chemistry and Biochemistry at University of California, Los Angeles, where she was hired in 1985 as the first female assistant professor in the department. As a PhD student in David Kearns’ laboratory at University of California, San Diego she published the first two-dimensional NMR spectra of short synthetic DNA duplexes. She was a Damon Runyon-Walter Winchell Postdoctoral fellow in the laboratory of Professor Alexander Rich at MIT, where she investigated structures of Z-DNA in solution by NMR. At UCLA, she pioneered the application of macromolecular NMR spectroscopy to the study of DNA and RNA structure, folding, and interactions with cations, drugs, and proteins. Her laboratory published the first NMR structures of DNA triplexes, quadruplexes, and aptamers, and her work has provided fundamental insights into DNA A-tract and protein induced bending, cation interactions with DNA, Hoogsteen base pairs, and drug binding to DNA. She has made major contributions in understanding RNA folding, dynamics, and function, including pseudoknots, aptamers, ribozymes, and riboswitches, and recognition of RNA by proteins including nucleolin and RNase III. Over the past 2 decades, the Feigon laboratory pioneered structure-function studies of telomerase, from solution NMR and X-ray crystal structures and dynamics studies of RNA and RNA–protein domains of human and Tetrahymena telomerase, to the first structure of a telomerase holoenzyme, by negative stain electron microscopy in 2013, and subsequent cryo-EM structures of telomerase and associated proteins. Today, her lab continues to investigate structural biology of telomerase as well as the transcriptional regulator 7SK RNP and other non-coding RNAs. For more about Juli, see her recent retrospective in J Mol Biol https://www.sciencedirect.com/science/article/pii/S0022283625001548.

Juli’s research has been recognized by awards including the Dupont Young Faculty Award (1985), National Science Foundation Presidential Young Investigator Award (1989), Glenn T. Seaborg Research Award (1992), Herbert Newby McCoy Research Award (1993, 2009, 2022), Fellow of the American Association for the Advancement of Science (2002), Member of the National Academy of Sciences (2009), Dorothy Crowfoot Hodgkin award of the Protein Society (2017), Biophysical Society Founders Award (2018), UCLA Academic Senate Diversity, Equity and Inclusion Research Award (2020), Glenn T. Seaborg Medal (2024), and Fellow of the International Society of Magnetic Resonance (2025).

About the lecture

Telomerase is an RNA-protein complex that maintains the 3’-ends of linear chromosomes, which would otherwise shorten with each round of replication. It is a highly regulated determinant of cellular aging, stem cell renewal, and tumorigenesis, and mutations in telomerase components are linked to numerous diseases. All telomerases contain a telomerase reverse transcriptase (TERT) and telomerase RNA (TER), which includes a template for synthesis of the telomere repeat (TTAGGG in humans) as well as other proteins essential for biogenesis and localization. My laboratory initiated structural studies of telomerase two decades ago, using NMR spectroscopy, when many of the components of the holoenzyme beyond TERT (telomerase reverse transcriptase) and TER (telomerase RNA) were not established, starting with TER domain structures including the discovery of an RNA major groove triplex within the essential telomerase RNA pseudoknot. Over the past decade our work has progressed to cryoEM structures of Tetrahymena and human telomerase, revealing new subunits, mechanistic insights, roles of the RNA, effects of disease mutations, and details of interactions at telomeres. I will present the evolution of our knowledge of the structural biology of telomerase, with emphasis on recent discoveries.