Feigon, Juli

Biochemistry

Biography

Dr. Feigon received her B.A. from Occidental College and her M.S. and Ph.D. (1982) from the University of California, San Diego where she studied with Dr. David Kearns. Her postdoctoral work was completed at the Massachusetts Institute of Technology, where she was a Damon Runyon-Walter Winchell Cancer Fund Postdoctoral Fellow with Dr. Alexander Rich from 1982-1985. Dr. Feigon joined the UCLA faculty in the Department of Chemistry and Biochemistry in 1985. She is currently Distinguished Professor of Biochemistry and holds the Christopher Foote Term Chair. She is a member of the UCLA-DOE institute of Genomics and Proteomics, the Molecular Biology Institute, and the California Nanosystems Institute. She is a recipient of the Dupont Young Faculty Award, National Science Foundation Presidential Young Investigator Award, Glenn T. Seaborg Research Award, Herbert Newby McCoy Research Award, is a Fellow of the American Association for the Advancement of Science and a Member of the National Academy of Sciences.

Dr. Feigon pioneered the use of NMR to determine structures and dynamics of DNA and RNA. As a graduate student (1976-1982) she used correlation NMR spectroscopy to investigate the interactions of >90 different drugs with DNA and also published the first two dimensional FT NMR spectra of DNA duplexes, demonstrating that NOESY and COSY data could be used reveal structural details. During her postdoctoral work (1982-1985) she used NMR to study the conversion of B-DNA to Z-DNA, correlating B-DNA resonances with Z-DNA resonances in one of the first examples of exchange spectroscopy applied to macromolecules. Dr. Feigon’s early work as a faculty member at UCLA (1985 on) was seminal in defining the conformational variability of DNA. She published the first 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. Her landmark 1992 structural studies of DNA quadruplexes formed by Oxytricha telomere repeats was seminal to the now burgeoning fields of G-quadruplex targeted anticancer and telomerase inhibiting drugs and DNA nanostructures. In the mid-1990s she began to turn her attention to understanding RNA folding and function, including studies of RNA aptamers, ribozymes, and riboswitches, and recognition of RNA by proteins. She solved the first solution structure of a riboswitch (preQ1) (2009) and set the standard for high resolution RNA structures determined by NMR. For all of this work, she has developed new NMR methods and applications for studying nucleic acids structure and dynamics, including assignments and detecting cation interactions. She has combined structural and functional studies of RNA-protein complexes to reveal essential determinants of protein recognition of single stranded and of double stranded RNA by RRMs and dsRBDs, respectively. She has made major contributions to understanding the structure, function, processing, and assembly of H/ACA RNPs, RNase III, and telomerase. Work on these projects as well as other non-coding and riboswitch RNAs is ongoing.

Her most recent work employs hybrid methods of NMR, Xray crystallography, and electron microscopy along with biochemistry to study structure, dynamics, and function of RNA and RNA-protein complexes. For the past decade a major focus of the laboratory has been on telomerase structure and function. Among her seminal achievements in this field was the first structure of a domain of telomerase RNA, a conserved pseudoknot containing a triple helix that is essential for activity (2005) and the structure of a telomerase RNA-protein complex that revealed a conformational change in the RNA required for telomerase assembly and a new protein-RNA recognition motif (2012). In 2013 she published the long awaited structure of a telomerase holoenzyme, determined by electron microscopy, with a model of the RNP catalytic core based on fitting of known NMR and crystal structures.

Dr. Feigon has on-going collaborations with Dr. Kathy Collins (telomerase biochemistry) and Dr. Z. Hong Zhou (electron microscopy) and a long-standing collaboration with Dr. Vladimir Sklenar (NMR methods development). Present and past collaborators include Drs. Michael Stone, Todd Yeates, Shu-ou Shan, Yehuda Tzfati, Tamas Kiss, Guillaume Chanfreau, Christopher Switzer, Duilio Cascio, Robert Clubb, Philippe Bouvet, Michelle Caizergues-Ferrer, Stephan Grzesiek, Wayne Hubbel, Peter Z. Qin, Ite Laird-Offringa, Reid Johnson, Daniel Neuhauser, Robert Griffin, Irvin S.Y. Chen, Jack Szostak, Frank Anet, David Eisenberg, Richard Lehrer, Peter Dervan, Larry Gold, Jacques van Boom, and Andrew H-J Wang.

Research Interests

Nucleic acid structure and function

RNA has increasingly been found to have a role in everything from regulation of transcription and translation to synthesis of the ends of chromosomes to enzymatic reactions. In order to do these things, RNA assumes a variety of shapes and often forms specific RNA-protein complexes. DNA can also adopt a variety of conformations besides the Watson-Crick double helix, and its interactions with proteins are vital to regulation of replication, transcription, and repair. My laboratory studies the structure and function of DNA and RNA primarily using multidimensional nuclear magnetic resonance (NMR) spectroscopy, which provides a method for determining the three-dimensional structures of macromolecules and to study their dynamics in solution. In addition to NMR spectroscopy, we use X-ray crystallography, small angle X-ray scattering, and cryoelectron microscopy for our structural studies. Structural and dynamics information is correlated with function using a variety of biochemical and molecular biological techniques, to provide insight into how these nucleic acids and nucleic acid-protein complexes work in the cell and how mutations in RNA and DNA can lead to disease. Currently, the research in my laboratory is focused on three major topics: (1) the structure and function of telomerase, (2) biogenesis of H/ACA RNPs, and (3) riboswitch structure and dynamics.

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Honors & Awards

  • Phi Beta Kappa, 1975
  • Damon Runyon-Walter Winchell Cancer Fund Postdoctoral Fellowship, November 1982-1985
  • National Research Service Award, National Institute of General Medical Sciences, National Institutes of Health, November 1984-December 1984
  • Dupont Young Faculty Award, 1985, 1986
  • Presidential Young Investigator, National Science Foundation, 1989-1994
  • Camille and Henry Dreyfus Teacher/Scholar Award, 1990
  • Glenn T. Seaborg Research Award, 1992
  • Herbert Newby McCoy Award, 1993
  • Fellow of the American Association for the Advancement of Science (AAAS), 2002
  • Council Member, International Society of Magnetic Resonance, 2008
  • Member, National Academy of Sciences, 2009
  • Dorothy Crowfoot Hodgkin Award, Protein Society, 2017
  • Founders Award, Biophysical Society, 2019
  • Faculty Award for Research DEI – Diversity, Equity, and Inclusion Award, UCLA Academic Senate, 2020
  • Herbert Newby McCoy Award, UCLA Chemistry & Biochemistry, 2022

Representative Publications

Below is the list of the most recent and selected publications.  For the full list, please visit here.

  • He Y, Feigon J.: “Telomerase structural biology comes of age”, Curr Opin Struct Biol. 76 (102446) (2022).[abstract]
  • He Y, Song H, Chan H, Liu B, Wang Y, Sušac L, Zhou ZH, Feigon J.: “Structure of Tetrahymena telomerase-bound CST with polymerase α-primase”, Nature. (2022) [abstract]
  • Liu B, He Y, Wang Y, Song H, Zhou ZH, Feigon J.: “Structure of active human telomerase with telomere shelterin protein TPP1”, Nature. 604(7906):578–583.(2022) [abstract]
  • Yang Y, Liu S, Egloff S, Eichhorn CD, Hadjian T, Zhen J, Kiss T, Zhou ZH, Feigon J.: “Structural basis of RNA conformational switching in the transcriptional regulator 7SK RNP”, Mol Cell. S1097-2765(22)00210-6. (2022) [abstract]
  • He Y, Wang Y, Liu B, Helmling C, Sušac L, Cheng R, Zhou ZH, Feigon J.: “Structures of telomerase at several steps of telomere repeat synthesis”, Nature. 593(7859):454-459. (2021). [PubMed]
  • Q. Zhang, N.-K. Kim, and J. Feigon: “The architecture of human telomerase RNA”, Proc. Natl. Acad. Sci. USA 10.1073/pnas.1100279108 (2011). [abstract]
  • B.-K. Koo, C.-J. Park, C.F. Fernandez, N. Chim, Y. Ding, G. Chanfreau, and J. Feigon: “Structure of H/ACA RNP protein Nhp2p reveals cis/trans isomerization of a conserved proline at the RNA and Nop10 binding interface”, J. Mol. Biol. 411, 927-942 (2011). [abstract]
  • Z. Wang, E. Hartman, K. Roy, G. Chanfreau, and J. Feigon: “Structure of a yeast RNase III dsRBD complex with a non-canonical RNA substrate provides insights into binding specificity of dsRBDs”, Structure 19, 999-1010 (2011). [abstract]
  • Q. Zhang, M. Kang, R.D. Peterson, and J. Feigon: “Comparison of solution and crystal structure of preQ1 riboswitch reveals calcium induced changes in conformation and dynamics”, J. Am. Chem. Soc. 133, 5190-5193 (2011). [abstract]
  • Q. Zhang, N.-K. Kim, R.D. Peterson, Z. Wang, and J. Feigon: “Structurally conserved five nucleotide bulge determines the overall topology of the core domain of human telomerase RNA”, Proc. Natl. Acad. Sci. USA 107, 18761-18768 (2010). [abstract]
  • N.-K. Kim, C.A. Theimer, J.R. Mitchell, K. Collins, and J. Feigon: “Effect of pseudouridylation on the structure and activity of the catalytically essential P6.1 hairpin in human telomerase RNA”, Nucleic Acids Res. 38, 6746-6756 (2010). [abstract]
  • M. Kang, R.D. Peterson, and J. Feigon: “Structural Insights into riboswitch control of the biosynthesis of queuosine, a modified nucleotide found in the anticodon of tRNA” Molecular Cell 33, 784-90 (2009) [abstract]
  • M. Singh, F.A. Gonzales, D. Cascio, N. Heckmann, G. Chanfreau, and J. Feigon: “Structure and functional studies of the CS domain of the essential H/ACA ribonucleoparticle assembly protein SHQ1” J. Biol. Chem. 284, 1906-16 (2008). [abstract]
  • N.K. Kim, Q. Zhang, J. Zhou, C.A. Theimer, R.D. Peterson, and J. Feigon: “Solution structure and dynamics of the wild-type pseudoknot of human telomerase RNA” J. Mol. Biol. 384, 1249-61 (2008) [abstract]
  • C.A. Theimer, B.E. Jady, N. Chim, P. Richard, K.E. Breece, T. Kiss, and J. Feigon: “Structural and functional characterization of human telomerase RNA processing and Cajal Body localization signals” Molecular Cell 27, 869-881 (2007). [abstract]
  • K. Januszyk, P.W. Li, V. Villareal, D. Branciforte, H. Wu, Y. Xie, J. Feigon, J.A. Loo, S.L. Martin, and R.T. Clubb: “Identification and solution structure of a highly conserved C-terminal domain required for the retrotransposition of Long Interspersed Nuclear Element-1” J. Biol. Chem. 282, 24893-24904(2007). [abstract]
  • H. Wu and J. Feigon: “H/ACA small nucleolar RNA pseudouridylation pockets bind substrate RNA to form three-way junctions that position the target U for modification” PNAS 104, 6655-6660 (2007). [abstract]
  • R.J. Richards, H. Wu, L. Trantirek, C.M. O’Connor, k. Collins, and J. Feigon: “Structural study of elements of Tetrahymena telomerase RNA stem-loop IV domain important for function” RNA 12, 1475-1485 (2006). [abstract]
  • C.A. Theimer and J. Feigon: “Structure and function of telomerase RNA”, Curr. Opin. Struct. Biol. 16, 307-318 (2006). [abstract]
  • R.J. Richards, C.A. Theimer, L.D. Finger, and J. Feigon: “Structure of the Tetrahymena thermophila telomerase RNA helix II template boundary element”, Nucleic Acids Res. 34, 816-825 (2006). [abstract]
  • M. Khanna, H. Wu, C. Johansson, M. Caizergues-Ferrer, and J. Feigon, “Structural study of the H/ACA snoRNP components Nop10p and the 3′ hairpin of U65 snoRNA”, RNA 12, 40-52 (2006) [abstract]
  • A.J. Dingley, R.D. Peterson, S. Grzesiek, and J. Feigon, “Characterization of the cation and temperature dependence of DNA quadruplex hydrogen bond properties using high-resolution NMR”, J. Am. Chem. Soc. 127, 14466-72 (2005). [abstract]
  • A.K. Henras, M. Sam, S.L. Hiley, H. Wu, J. Feigon, T.R. Hughes, and G.F. Chanfreau: “Biochemical and genomic and analysis of substrate recognition by the double stranded RNA binding domain of yeast RNase III”, RNA 11, 1225-1237 (2005). [abstract]
  • P.Z. Qin, J. Feigon, and W. Hubbell: “Site-directed spin labeling studies reveal a coupled mechanism in the formation of the GAAA tetraloop/receptor RNA tertiary interaction”, J. Mol. Biol. 351, 1-8 (2005). [abstract]
  • H. Wu, L.D. Finger, J. Feigon: “Structure determination of Protein/RNA complexes by NMR”, in Methods in Enzymol. (T.L. James, ed.) Academic Press, 394, 525-545 (2005). [abstract]
  • C.A. Theimer, C.A. Blois, and J. Feigon: “Structure of the human telomerase RNA pseudoknot reveals conserved tertiary interactions essential for function”, Mol. Cell 17, 671-682 (2005). [abstract]
  • M. Kamionka and J. Feigon: “Structure of the XPC binding domain of hHR23A reveals hydrophobic patches for protein interaction”, Protein Science, 13, 2370-2377 (2004). [abstract]
  • J. Feigon and C. Bustamante: “Nucleic acids – controlling biology and controlled by biophysics” Curr. Opin. Struct. Biol., 14, 333-334 (2004).
  • L.D. Finger, C. Johansson, B. Rinaldi, P. Bouvet, and J. Feigon “Contributions of the RBDs and linker domains and RNA structure to the specificity and affinity of the nucleolin RBD12/NRE interaction” Biochemistry, 43, 6937-6947 (2004). [abstract]
  • H. Wu, A. Henras, G. Chanfreau, and J. Feigon: “Structural basis for recognition of the AGNN tetraloop RNA fold by the double-stranded RNA binding domain of Rnt1p Rnase III”, Proc. Natl. Acad. Sci. USA, 101, 8307-8312 (2004). [abstract]
  • C. Johansson, L.D. Finger, L. Trantirek, T.D. Mueller, S. Kim, I.A. Laird-Offringa, and J. Feigon: “Solution structure of the complex formed by the two N-terminal RNA-binding domains of nucleolin and a pre-rRNA target”, J. Mol. Biol., 337, 799-816 (2004). [abstract]
  • T.D. Mueller, M. Kamionka, and J. Feigon: “Specificity of the interaction between UBA domains and ubiquitin”, J. Biol. Chem., 279, 11926-11936 (2004). [abstract]
  • R. Stefl, H. Wu, S. Ravindranathan, V. Sklenár, and J. Feigon: “DNA A-tract bending in three dimensions: Solving the dA4T4 versus dT4A4 conundrum”, Proc. Natl. Acad. Sci. USA, 101, 1177-1182 (2004). [abstract]
  • R.D. Peterson, C.A. Theimer, H. Wu, and J. Feigon: “New Applications of 2D Filtered/Edited NOESY for Assignment and Structure Elucidation of RNA and RNA-Protein Complexes”, J. Biomol. NMR, 28, 59-67 (2004). [abstract]
  • C.A. Theimer, L.D, Finger, and J. Feigon: “YNMG tetraloop formation by a dyskeratosis congenita mutation in human telomerase RNA”, RNA, 9, 1446-1455 (2003). [abstract]
  • L.D. Finger, L. Trantirek, C. Johansson, and J. Feigon: “Solution structures of stem-loop RNAs that bind to the two N-terminal RNA-binding domains of nucleolin”, Nucleic Acids Res. 31, 6461-6472 (2003). [abstract]
  • T.M. Mueller and J. Feigon: “Structural determinants for the binding of ubiquitin-like domains to the proteasome”, EMBO J., 22, 4634-4645 (2003). [abstract]
  • P.Z. Qin, K. Hideg, J. Feigon, and W.L. Hubbell: “Monitoring RNA base structure and dynamics using site-directed spin labeling”, Biochemistry, 42, 6772-6783 (2003). [abstract]
  • C.A. Theimer, L.D. Finger, L. Trantirek, and J. Feigon: “Mutations linked to dyskeratosis congenita cause dynamic changes in telomerase RNA structure”, Proc. Natl. Acad. Sci. USA, 100, 449-454 (2003). [abstract]