- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Viral Infections and Immunology Research
- Cancer-related molecular mechanisms research
- RNA regulation and disease
- Advanced biosensing and bioanalysis techniques
- Protein Structure and Dynamics
- HIV Research and Treatment
- Molecular Biology Techniques and Applications
- DNA Repair Mechanisms
- Plant Virus Research Studies
- Hepatitis C virus research
- CRISPR and Genetic Engineering
- Bacterial Genetics and Biotechnology
- Chemical Synthesis and Analysis
- thermodynamics and calorimetric analyses
- Telomeres, Telomerase, and Senescence
- Electron Spin Resonance Studies
- Nitric Oxide and Endothelin Effects
- RNA Interference and Gene Delivery
- Integrated Circuits and Semiconductor Failure Analysis
- Protist diversity and phylogeny
- interferon and immune responses
University of Wisconsin–Madison
2016-2025
Center for Information Technology
2008
Argonne National Laboratory
2008
National Institutes of Health
2008
Mayo Clinic
2007
Resonance Research (United States)
2006
University of Missouri
2003
University of California, Los Angeles
1997-2001
Doheny Eye Institute
2001
University of Vermont
1993-1996
Just as proteins form distinct structural motifs, certain structures are commonly adopted by RNA molecules. Amongst the most prevalent is pseudoknot.
RNA molecules adopt specific three-dimensional structures critical to their function. Many essential metabolic processes, including protein synthesis and splicing, are carried out by with elaborate tertiary (e.g. 3QIQ, right). Indeed, the ribosome self-splicing introns complex machines. But even coding regions in messenger RNAs viral flanked highly structured untranslated regions, which provide regulatory information necessary for gene expression.RNA structure is defined as arrangement of...
The U2/U6 snRNA complex is a conserved and essential component of the active spliceosome that interacts with pre-mRNA substrate protein splicing factors to promote catalysis. Here we have elucidated solution structure 111-nucleotide using an approach integrates SAXS, NMR, molecular modeling. contains three-helix junction forms extended “Y” shape. U6 internal stem–loop (ISL) continuous stack Helices Ib, Ia, III. coaxial stacking Helix Ib on ISL configuration similar Domain V in group II...
The human immunodeficiency virus (HIV) requires a programmed −1 ribosomal frameshift for Pol gene expression. HIV site consists of heptanucleotide slippery sequence (UUUUUUA) followed by spacer region and downstream RNA stem–loop structure. Here we investigate the role structure in promoting frameshift. was systematically altered to decouple contributions local overall thermodynamic stability towards efficiency. No correlation between efficiency is observed. In contrast, there strong first...
Escherichia coli DksA is a transcription factor that binds to RNA polymerase (RNAP) without binding DNA, destabilizing RNAP–promoter interactions, sensitizing RNAP the global regulator ppGpp, and regulating of several hundred target genes, including those encoding rRNA. Previously, we described promoter sequences kinetic properties account for DksA's specificity, but how exerts its effects on has remained unclear. To better understand mechanism action, incorporated benzoyl-phenylalanine at...
RecQ helicases unwind remarkably diverse DNA structures as key components of many cellular processes. How enzymes accommodate different substrates in a unified mechanism that couples ATP hydrolysis to unwinding is unknown. Here, the X-ray crystal structure Cronobacter sakazakii catalytic core domain bound duplex with 3' single-stranded extension identifies two DNA-dependent conformational rearrangements: winged-helix pivots ∼90° close onto DNA, and conserved aromatic-rich loop remodeled bind...
The GNRA (N: any nucleotide; R: purine) tetraloop/receptor interaction is believed to be one of the most frequently occurring tertiary motifs in RNAs, but an isolated complex has not been identified solution. In present work, site-directed spin labeling applied detect formation and estimate free energy interaction. For this purpose, GAAA was chosen as a model system. A method developed place nitroxide labels at specific backbone locations RNA hairpin containing tetraloop. Formation monitored...
Substrate recognition by the hairpin ribozyme has been proposed to involve two short intermolecular helices, termed helix 1 and 2. We have used a combination of three methods (cleavage mismatched substrates, in vitro selection, site-specific mutational analysis) systematically determine substrate rules for this RNA enzyme. Assays measuring cleavage trans under multiple turnover conditions were conducted using wild-type substrates containing mismatches all sites potentially recognized...
Programmed -1 translational frameshifting is an essential event in the replication cycle of HIV. Frameshifting required for expression viral Pol proteins, and drug-like molecules that target this process may inhibit HIV replication. A small molecule stimulator HIV-1 inhibitor replication, DB213 (RG501), was previously discovered from a high-throughput screen. However, mechanistic basis compound's effects unknown, to date no structural information exists effectors frameshifting. Here, we...
NMR spectroscopy is a powerful technique for determining structural and functional features of biomolecules in physiological solution as well observing their intermolecular interactions real-time. However, complex steps associated with its practice have made the approach daunting non-specialists. We introduce an platform that makes biomolecular much more accessible by integrating tools, databases, web services, video tutorials can be launched simple installation NMRFAM software packages or...
In eukaryotes, the process of intron removal from nuclear pre-mRNA is performed by spliceosome, a dynamic molecular machine composed small ribonucleoproteins (snRNPs; U1, U2, U4, U5, and U6) dozens other protein splicing factors. The U6 snRNP contains snRNA proteins Prp24 Lsm2-8 heteroheptamer. A key feature modified 3' end, which in S. cerevisiae (yeast) phosphate. plays an essential role splicing, must be completely disassembled for to occur. Once finished, then reassembled participate...
Abstract G-quadruplex (G4) is a guanine-rich secondary structure found in DNA and RNA involved various biological roles. Recently, non-canonical (rG4), known as poly(UG) (pUG) fold, was discovered Caenorhabditis elegans. This unique to induce interference (RNAi) upon recruitment of RNA-dependent polymerase (RdRP), resulting trans-generational gene silencing. Herein, we develop novel L-RNA aptamer, L-apt3.1, that binds the pUG fold. We uncover L-apt3.1 consists parallel rG4 structural motif,...