Professor
Department of Biochemistry and Biophysics
Primary Thematic Area
Secondary Thematic Area
Research Summary
RNA-Protein Complexes
+1 415 476-9994
The Frankel Lab focuses on RNA-protein recognition and the assembly of RNA-based regulatory complexes. We use biochemistry, structural methods, proteomics, and virology to investigate two essential regulatory complexes in HIV: the viral Tat protein and its interactions with the host transcription machinery, and the viral Rev protein and its interactions with host nuclear export complexes. In concert with proteomic studies of HIV-human protein complexes, our studies have led to an understanding of how the virus has evolved adaptable protein interfaces to hijack these two host machines and establish a unique regulatory circuit that drives gene expression during the HIV life cycle.
Websites
Publications
The HIV-1 Nuclear Export Complex Reveals the Role of RNA in Crm1 Cargo Recognition.
bioRxiv : the preprint server for biology
Enhanced NF-κB activation via HIV-1 Tat-TRAF6 cross-talk.
Science advances
Phosphoregulation of Phase Separation by the SARS-CoV-2 N Protein Suggests a Biophysical Basis for its Dual Functions.
Molecular cell
A Quantitative Genetic Interaction Map of HIV Infection.
Molecular cell
ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.
Cell host & microbe
Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability.
Scientific reports
Discovery of a Branched Peptide that Recognizes the Rev Response Element (RRE) RNA and Blocks HIV-1 Replication.
Journal of medicinal chemistry
Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription.
Annual review of virology
Identification and Optimization of Thienopyridine Carboxamides as Inhibitors of HIV Regulatory Complexes.
Antimicrobial agents and chemotherapy
PJA2 ubiquitinates the HIV-1 Tat protein with atypical chain linkages to activate viral transcription.
Scientific reports
Oligomeric viral proteins: small in size, large in presence.
Critical reviews in biochemistry and molecular biology
A structurally plastic ribonucleoprotein complex mediates post-transcriptional gene regulation in HIV-1.
Wiley interdisciplinary reviews. RNA
Selective Targeting of Cells via Bispecific Molecules That Exploit Coexpression of Two Intracellular Proteins.
ACS chemical biology
Transition step during assembly of HIV Tat:P-TEFb transcription complexes and transfer to TAR RNA.
Molecular and cellular biology
Transcription control by long non-coding RNAs.
Transcription
GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data.
BMC bioinformatics
Comparative analysis of RNA/protein dynamics for the arginine-rich-binding motif and zinc-finger-binding motif proteins encoded by HIV-1.
Biophysical journal
An SF1 affinity model to identify branch point sequences in human introns.
Nucleic acids research
Structural basis for cooperative RNA binding and export complex assembly by HIV Rev.
Nature structural & molecular biology
Purification and characterization of HIV-human protein complexes.
Methods (San Diego, Calif.)
HIV Rev response element (RRE) directs assembly of the Rev homooligomer into discrete asymmetric complexes.
Proceedings of the National Academy of Sciences of the United States of America
RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation.
Nature structural & molecular biology
Tat acetylation modulates assembly of a viral-host RNA-protein transcription complex.
Proceedings of the National Academy of Sciences of the United States of America
A solution to limited genomic capacity: using adaptable binding surfaces to assemble the functional HIV Rev oligomer on RNA.
Molecular cell
Targeting tat inhibitors in the assembly of human immunodeficiency virus type 1 transcription complexes.
Journal of virology
ISFOLD: structure prediction of base pairs in non-helical RNA motifs from isostericity signatures in their sequence alignments.
Journal of biomolecular structure & dynamics
An alpha-helical peptidomimetic inhibitor of the HIV-1 Rev-RRE interaction.
Journal of the American Chemical Society
A simple motif for protein recognition in DNA secondary structures.
Journal of molecular biology
Viral RNA gymnastics.
Nature chemical biology
Localized influence of 2'-hydroxyl groups and helix geometry on protein recognition in the RNA major groove.
Biochemistry
A single intermolecular contact mediates intramolecular stabilization of both RNA and protein.
Proceedings of the National Academy of Sciences of the United States of America
Selection of TAR RNA-binding chameleon peptides by using a retroviral replication system.
Journal of virology
Ab initio interaction energies of hydrogen-bonded amino acid side chain[bond]nucleic acid base interactions.
Journal of the American Chemical Society
Recognition of nucleic acid bases and base-pairs by hydrogen bonding to amino acid side-chains.
Journal of molecular biology
Structural diversity and isomorphism of hydrogen-bonded base interactions in nucleic acids.
Journal of molecular biology
Replication of human immunodeficiency viruses engineered with heterologous Tat-transactivation response element interactions.
Journal of virology
Selection of RRE RNA binding peptides using a kanamycin antitermination assay.
RNA (New York, N.Y.)
Design of RNA-binding proteins and ligands.
Current opinion in structural biology
Recognition of RNA branch point sequences by the KH domain of splicing factor 1 (mammalian branch point binding protein) in a splicing factor complex.
Molecular and cellular biology
Molecular dynamics and binding specificity analysis of the bovine immunodeficiency virus BIV Tat-TAR complex.
Biophysical journal
Structural characterization of the complex of the Rev response element RNA with a selected peptide.
Chemistry & biology
Structure-based design of a dimeric RNA-peptide complex.
The EMBO journal
An RNA-binding chameleon.
Molecular cell
Fitting peptides into the RNA world.
Current opinion in structural biology
Screening RNA-binding libraries by transcriptional antitermination in bacteria.
Methods in enzymology
Screening RNA-binding libraries using Tat-fusion system in mammalian cells.
Methods in enzymology
Screening in vivo for RNA-binding peptides from combinatorial libraries.
Nucleic acids symposium series
Using peptides as models of RNA-protein interactions.
Methods in enzymology
If the loop fits...
Nature structural biology
Structure-based design of an RNA-binding zinc finger.
Proceedings of the National Academy of Sciences of the United States of America
RNase treatment of yeast and mammalian cell extracts affects in vitro substrate methylation by type I protein arginine N-methyltransferases.
Biochemical and biophysical research communications
In vivo selection of RNA-binding peptides from combinatorial libraries.
Nucleic acids symposium series
Screening RNA-binding libraries using a bacterial transcription antitermination assay.
Methods in molecular biology (Clifton, N.J.)
Altering the context of an RNA bulge switches the binding specificities of two viral Tat proteins.
Biochemistry
A novel glutamine-RNA interaction identified by screening libraries in mammalian cells.
Proceedings of the National Academy of Sciences of the United States of America
HIV-1: fifteen proteins and an RNA.
Annual review of biochemistry
Molding a peptide into an RNA site by in vivo peptide evolution.
Proceedings of the National Academy of Sciences of the United States of America
Alpha helix-RNA major groove recognition in an HIV-1 rev peptide-RRE RNA complex.
Science (New York, N.Y.)
Assignment and modeling of the Rev Response Element RNA bound to a Rev peptide using 13C-heteronuclear NMR.
Journal of biomolecular NMR
Identification of two novel arginine binding DNAs.
The EMBO journal
Solution structure of a bovine immunodeficiency virus Tat-TAR peptide-RNA complex.
Science (New York, N.Y.)
Structural variety of arginine-rich RNA-binding peptides.
Proceedings of the National Academy of Sciences of the United States of America
A peptide interaction in the major groove of RNA resembles protein interactions in the minor groove of DNA.
Proceedings of the National Academy of Sciences of the United States of America
Increased cellular uptake of the human immunodeficiency virus-1 Tat protein after modification with biotin.
Analytical biochemistry
Interaction of HIV Rev peptides with the Rev response element RNA.
Nucleic acids symposium series
Binding of an HIV Rev peptide to Rev responsive element RNA induces formation of purine-purine base pairs.
Biochemistry
An RNA-binding peptide from bovine immunodeficiency virus Tat protein recognizes an unusual RNA structure.
Biochemistry
Factors associated with airway colonisation and invasion due to Klebsiella spp.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
Role of RNA structure in arginine recognition of TAR RNA.
Proceedings of the National Academy of Sciences of the United States of America
Electrostatic interactions modulate the RNA-binding and transactivation specificities of the human immunodeficiency virus and simian immunodeficiency virus Tat proteins.
Proceedings of the National Academy of Sciences of the United States of America
The importance of being flexible.
Proceedings of the National Academy of Sciences of the United States of America
Peptide models of the Tat-TAR protein-RNA interaction.
Protein science : a publication of the Protein Society
Circular dichroism studies suggest that TAR RNA changes conformation upon specific binding of arginine or guanidine.
Biochemistry
Conformation of the TAR RNA-arginine complex by NMR spectroscopy.
Science (New York, N.Y.)
Activation of HIV transcription by Tat.
Current opinion in genetics & development
Specific binding of arginine to TAR RNA.
Proceedings of the National Academy of Sciences of the United States of America
Specific binding of a basic peptide from HIV-1 Rev.
The EMBO journal
The Arginine Fork: Correction.
Science
Endocytosis and targeting of exogenous HIV-1 Tat protein.
The EMBO journal
Arginine-mediated RNA recognition: the arginine fork.
Science (New York, N.Y.)
The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation.
Proceedings of the National Academy of Sciences of the United States of America
Analysis of arginine-rich peptides from the HIV Tat protein reveals unusual features of RNA-protein recognition.
Genes & development
Role of arginine 180 and glutamic acid 177 of ricin toxin A chain in enzymatic inactivation of ribosomes.
Molecular and cellular biology
Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1.
Science (New York, N.Y.)
Activity of synthetic peptides from the Tat protein of human immunodeficiency virus type 1.
Proceedings of the National Academy of Sciences of the United States of America
Selection and characterization of ricin toxin A-chain mutations in Saccharomyces cerevisiae.
Molecular and cellular biology
Dimerization of the tat protein from human immunodeficiency virus: a cysteine-rich peptide mimics the normal metal-linked dimer interface.
Proceedings of the National Academy of Sciences of the United States of America
Tat protein from human immunodeficiency virus forms a metal-linked dimer.
Science (New York, N.Y.)
Systematic analysis of possible hydrogen bonds between amino acid side chains and B-form DNA.
Journal of biomolecular structure & dynamics
Restriction and modification enzymes detect no allosteric changes in DNA with bound lac repressor or RNA polymerase.
Journal of molecular biology