About

Juli F. Feigon is a Distinguished Professor of Biochemistry at UCLA and holds the Christopher S. Foote Endowed Chair. She received her B.A. from Occidental College and her M.S. and Ph.D. from the University of California, San Diego, where she studied with Dr. David Kearns. Her postdoctoral work was completed at MIT under Dr. Alexander Rich, focusing on NMR studies of DNA. Since joining UCLA in 1985, Dr. Feigon has pioneered the use of NMR to determine structures and dynamics of DNA and RNA, publishing foundational work on DNA interactions, conformational variability, and structures of DNA triplexes, quadruplexes, and aptamers. Her research has significantly contributed to understanding DNA and RNA structure-function relationships, including the first solution structure of a riboswitch and insights into RNA-protein complexes. Her recent work employs hybrid methods such as NMR, X-ray crystallography, and electron microscopy to study nucleic acids and their complexes, with a major focus on telomerase structure and function. Dr. Feigon has received numerous awards and honors, including election to the National Academy of Sciences, and is recognized for her fundamental contributions to nucleic acid structural biology.

Research topics

• Chemistry
• Biology
• Crystallography
• Stereochemistry
• Cell biology

Selected publications

• HEXIM1 inter-monomer autoinhibition governs 7SK RNA binding specificity and P-TEFb inactivation

  Nature Communications · 2026-01-15

  articleOpen accessSenior authorCorresponding

  Hexim proteins are key RNA-dependent regulators of eukaryotic transcription through 7SK-dependent sequestration and inactivation of the kinase P-TEFb (Cdk9-CyclinT1/2) in the 7SK RNP. P-TEFb activity drives release of RNA polymerase II from promoter-proximal pausing for eukaryotic and HIV-1 transcription. The molecular mechanism by which 7SK binding overcomes an intrinsic Hexim autoinhibition for subsequent P-TEFb inactivation has remained unresolved. Here, using NMR and biophysical methods we demonstrate that Hexim1 homodimer engages two high-affinity sites on 7SK RNA. This dual-site binding triggers a conformational rearrangement in Hexim1's disordered central region that unmasks the Cdk9-binding site, which is otherwise sequestered within an inter-monomer dimer interface. These findings reveal how Hexim autoinhibition dictates its specificity for 7SK RNA and prevents premature P-TEFb inhibition in the absence of 7SK, thereby providing a mechanistic understanding of Hexim/P-TEFb assembly into the 7SK RNP and further considerations for understanding Hexim-Tat competition during viral transcription.

  PublisherOA PDFDOI

• Cryo-EM structures reveal a conserved architecture for raiA noncoding RNA

  Nucleic Acids Research · 2026-02-24

  articleOpen accessSenior author

  RaiA motif RNA is a family of bacterial noncoding RNAs (ncRNAs) found in over 2700 bacterial species. Although its cellular abundance is comparable to that of rRNAs and tRNAs in the human pathogen Clostridioides difficile and its knockout results in pronounced phenotypes, its function remains unknown. Sequence conservation analysis predicted a consensus secondary structure of raiA motif RNA with several major subtypes that differ in the number and composition of stems. Here, we present cryogenic electron microscopy (cryo-EM) structures of three raiA motif RNAs from three bacterial species, one from each subtype, at 3.0-3.5 Å resolution, as well as a minimal variant with 113 nucleotides at ∼8 Å resolution. Comparison of the structures reveals a conserved architecture, with a compact core comprising stems P3a-P3b bent by an asymmetric internal loop, P4, pseudoknot 1 (PK1), and PK2 with unusual tertiary interactions. While most of the peripheral stems vary, the length, structure, and tertiary interactions of the closing P1 are remarkably conserved, suggesting an essential role. Our study defines the conserved structural framework of raiA motif RNAs and provides a foundation for structure-based functional studies. This work also highlights the utility of cryo-EM for de novo structure determination of ncRNAs.

  PublisherDOI

• Structural biology of telomerase mechanism and interactions at telomeres

  Structural Dynamics · 2025-03-01

  articleOpen access1st authorCorresponding

  Telomerase is a unique RNA-containing reverse transcriptase that synthesizes the DNA at the 3’-ends of telomeres, the structures at the ends of linear chromosomes. It is a highly regulated determinant of tumorigenesis, cellular aging, and stem cell renewal. All telomerases contain a catalytic core comprising telomerase reverse transcriptase (TERT) and telomerase RNA (TER), along with other proteins involved in biogenesis, assembly, and activation. TER includes a template complementary to ∼1.5 telomere repeats used by TERT to repetitively synthesize the telomere repeat (dTTGGGG in Tetrahymena, dTTAGGG in human), but other regions of TER are required for activity. Human telomerase is recruited to the 3’-ends of telomeres by TPP1–POT1 to processively synthesize multiple telomeric repeats (G-strand). The complementary C-strand is subsequently synthesized by DNA polymerase a–primase (PolaPrim) in concert with CTC1–STN1–TEN1 (CST). We have used cryo-electron microscopy studies combined with NMR spectroscopy and biochemical methods on Tetrahymena and human telomerase to investigate structure, assembly, and the mechanism of G-strand telomeric DNA repeat addition [1,2], interactions of TPP1/p50 with telomerase for recruitment and activation [1,2], and interactions of CST with telomerase and PolaPrim for C-strand synthesis [3]. For human telomerase, results also reveal that numerous disease mutations would disrupt interactions at the TER–TER interface, highlighting their importance for function [3]. Highlights of this recent work from our laboratory will be presented.

  PublisherDOI

• BPS2025 - HEXIM1 homodimer binds two sites on 7SK RNA to release the autoinhibition of P-TEFb inactivation

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• BPS2025 - Cryo-EM structures of 50–80 kDa bacterial non-coding RNAs at 3.0–3.5 Å resolution

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• 7SK SL1-pII RNA

  Open MIND · 2025-01-01

  datasetSenior author

• A (Scientific) Lifetime Affair With Nucleic Acids

  Journal of Molecular Biology · 2025-03-12 · 3 citations

  reviewOpen access1st authorCorresponding
  PublisherOA PDFDOI

• How short peptides disassemble tau fibrils in Alzheimer’s disease

  Nature · 2025-07-09 · 13 citations

  articleOpen access
  PublisherOA PDFDOI

• How short peptides can disassemble ultra‐stable tau fibrils extracted from Alzheimer’s disease brain by a strain‐relief mechanism

  Alzheimer s & Dementia · 2024-12-01

  articleOpen access

  Abstract Background Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer’s disease (AD). Previously we found that in vitro the D‐peptide D‐TLKIVWC fragments tau fibrils from AD brains (AD‐tau) into benign segments, whereas its six‐residue analog D‐TLKIVW cannot. However, the underlying fragmentation mechanism remains unknown, preventing the further development of this type of drug candidate for AD. Method To understand the necessity of the cysteine residue of D‐TLKIVWC in fragmenting AD‐tau, we designed a series of peptides of sequence D‐TLKIVWX varying only at the seventh residue, X. To better understand the fragmentation process of AD‐tau, we conducted a time‐course dot blot and EM experiment. We determined the structures of D‐TLKIVWX amyloid‐like fibrils by atomic force microscopy and cryo‐electron microscopy. We studied the complexes of D‐TLKIVWX (X = I, S, R) with AD‐tau by cryo‐electron microscopy and confirmed the binding site between D‐TLKIVWX and Tau through NMR. Result These D‐TLKIVWX candidates showed various efficacies in fragmenting AD‐tau in vitro, in which X = Ile was the best performer. From electron microscopy, we discovered that D‐TLKIVWX peptides form amyloid‐like fibrils themselves, and from atomic force microscopy we learned that these fibrils have a right‐handed helical twist, in contrast to the left‐handed helical twist of AD‐tau. From cryo‐EM we learned that D‐TLKIVWX protofilaments bind to tau fibrils of opposing twist. Conclusion We find that the amyloid‐like, fibril‐forming property of D‐TLKIVWX contributes to the fragmentation of AD‐tau fibrils. We propose the strain‐relief mechanism of fragmentation and believe the fragmentation of AD‐tau fibrils is driven by the release of torsion in D‐TLKIVWX protofilaments.

  PublisherOA PDFDOI

• HEXIM1 inter-monomer autoinhibition governs 7SK RNA binding specificity and P-TEFb inactivation

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-13 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Hexim proteins are RNA-dependent regulators whose main target is 7SK long non-coding RNA, a major regulator of eukaryotic mRNA transcription. 7SK RNPs control available intracellular concentrations of the kinase P-TEFb (Cdk9-CyclinT1/2) by sequestering it in an inactive form. Active P-TEFb phosphorylates NELF, DSIF, and the RNA polymerase II CTD to transition it from promoter-proximal pausing to productive elongation. P-TEFb associates with 7SK RNP via Hexim, which directly binds 7SK RNA. However, free Hexim is in an autoinhibited state that cannot inactivate P-TEFb, and how Hexim autoinhibition is released by 7SK remains unknown. Here, we show that one Hexim1 homodimer binds two sites on linear 7SK RNA in a manner that exposes the Cdk9 binding sites, which are otherwise masked within the autoinhibited dimer. These results provide mechanistic insights into Hexim-RNA specificity and explain how P-TEFb can be effectively regulated to respond to changing levels of transcriptional signaling.

  PublisherOA PDFDOI

Recent grants

• Structure and Function of Human Telomerase

  NIH · $8.0M · 1992–2019

• NMR Studies of RNA Enzymes

  NSF · $360k · 2001–2005

• NIH Grant S10RR015754

  NIH · $500k · 2002

• Structural biology of 7SK RNP and its interaction with HIV-1 Tat

  NIH · $2.4M · 2020–2026

• 800 MHz NMR Console and Cryoprobe Replacement

  NIH · $1.1M · 2018–2020

Frequent coauthors

• Andrew J. Dingley

  Heinrich Heine University Düsseldorf

  42 shared

• Stephan Grzesiek

  University of Basel

  42 shared

• Robert D. Peterson

  Oakton Community College

  36 shared

• Michael Barfield

  University of Florida

  32 shared

• James E. Masse

  25 shared

• Vladimı́r Sklenář

  23 shared

• Z. Hong Zhou

  University of California System

  21 shared

• Thorsten Dieckmann

  University of Waterloo

  21 shared

Awards & honors

• Phi Beta Kappa, 1975
• Damon Runyon-Walter Winchell Cancer Fund Postdoctoral Fellow…
• National Research Service Award, National Institute of Gener…
• Dupont Young Faculty Award, 1985, 1986
• Presidential Young Investigator, National Science Foundation…