A5023009930- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- RNA Research and Splicing
- Fish Biology and Ecology Studies
- RNA modifications and cancer
- Ichthyology and Marine Biology
- HIV/AIDS drug development and treatment
- Fish Ecology and Management Studies
- Viral Infections and Immunology Research
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- SARS-CoV-2 and COVID-19 Research
- Cancer-related gene regulation
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- Neurobiology and Insect Physiology Research
- Hepatitis C virus research
- Protein Structure and Dynamics
- Spider Taxonomy and Behavior Studies
- Clostridium difficile and Clostridium perfringens research
- Biochemical and Structural Characterization
- PI3K/AKT/mTOR signaling in cancer
- MicroRNA in disease regulation
- SARS-CoV-2 detection and testing
- Bacterial Identification and Susceptibility Testing
University of Missouri
2016-2025
Chengdu University of Traditional Chinese Medicine
2025
Woodlands Health Campus
2023
Panzhihua Central Hospital
2021
University of Maryland, Baltimore County
2011-2019
Howard Hughes Medical Institute
2011-2015
Rusangu University
2000
Structural signals that direct HIV packaging During the viral replication cycle of HIV, unspliced dimeric RNA genomes are efficiently packaged into new virions at host cell membrane. Packaging is directed by a region start genome, 5′ leader. The architecture leader remains controversial. Keane et al. developed nuclear magnetic resonance methods to determine structure 155-nucleotide-long can packaging. shows how binds protein directs packaging, selected for and translation suppressed when...
The 5'-leader of the HIV-1 genome regulates multiple functions during viral replication via mechanisms that have yet to be established. We developed a nuclear magnetic resonance approach enabled direct detection structural elements within intact leader (712-nucleotide dimer) are critical for packaging. Residues spanning gag start codon (AUG) form hairpin in monomeric and base pair with residues unique-5' region (U5) dimer. U5:AUG formation promotes dimerization by displacing exposing...
Significance A nucleotide-specific 2 H-edited NMR approach was used to determine the nature of intermolecular interface in intact, dimeric HIV type-1 (HIV-1) 5′-leader RNA (230 kD). The studies distinguish between previously proposed extended duplex and kissing hairpin models identify additional interaction sites. one-dimensional method that allows temporal monitoring base-pair formation revealed observed “extended dimer interface” forms rapidly, even absence chaperones. In addition...
Appended to the 5' end of nascent RNA polymerase II transcripts is 7-methyl guanosine (m7G-cap) that engages nuclear cap-binding complex (CBC) facilitate messenger (mRNA) maturation. Mature mRNAs exchange CBC for eIF4E, rate-limiting translation factor controlled through mTOR. Experiments in immune cells have now documented HIV-1 incompletely processed exhibited hypermethylated m7G-cap and down-regulation trimethylguanosine synthetase-1-reduced infectivity virion protein synthesis by several...
The Biological Magnetic Resonance Data Bank contains NMR chemical shift depositions for 132 RNAs and RNA-containing complexes. We have analyzed the (1)H shifts reported non-exchangeable protons of residues that reside within A-form helical regions these RNAs. analysis focused on central base pair a stretch three adjacent pairs (BP triplets), included both Watson-Crick (WC; G:C, A:U) G:U wobble pairs. Chemical values were all 4(3) possible WC-BP triplets, as well 137 additional triplets...
Coronaviruses (CoVs) are positive-stranded RNA viruses that infect humans and animals. Infection by CoVs such as HCoV-229E, -NL63, -OC43 -HKU1 leads to the common cold, short lasting rhinitis, cough, sore throat fever. However, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East (MERS-CoV), newest SARS-CoV-2 (the causative agent of COVID-19) lead severe deadly diseases with mortality rates ranging between ~1 35% depending on factors age pre-existing conditions. Despite...
The paradigm protein synthesis rate is regulated by structural complexity of the 5'untranslated region (UTR) derives from bacterial and other riboswitches. In-solution, HIV-1 5'UTR forms two interchangeable long-range nucleotide (nt) -pairings, one sequesters gag start codon promoting dimerization while dimer initiation signal preventing dimerization. While effect these nt-pairings on packaging has been documented their authentic HIV translation in cellulo remained elusive until now....
RNA aptamers that bind HIV-1 reverse transcriptase (RT) inhibit RT in enzymatic and viral replication assays. Some from only a few clades, while others show broad-spectrum inhibition. Biophysical determinants of recognition specificity are poorly understood. We investigated the interface between UCAA-family aptamer. SAR hydroxyl radical probing identified aptamer structural elements critical for inhibition established role signature UCAA bulge motif RT-aptamer interaction. HDX footprinting...
Abstract The discovery of ribozymes has inspired exploration RNA’s potential to serve as primordial catalysts in a hypothesized RNA world. Modern oxidoreductase enzymes employ differential binding between reduced and oxidized forms redox cofactors alter cofactor reduction enhance the enzyme’s catalytic capabilities. utility affinity been underexplored chemical strategy for RNA. Here we show an aptamer that preferentially binds flavin over markedly shifts by −40 mV, similar oxidoreductases....
Abstract HIV-1 reverse transcription initiates at the primer binding site (PBS) in viral genomic RNA (gRNA). Although structure of PBS-segment undergoes substantial rearrangement upon tRNALys3 annealing, proper folding during gRNA packaging is important as it ensures loading beneficial host factors. DHX9/RNA helicase A (RHA) recruited to enhance processivity transcriptase. Because molecular details interactions have yet be defined, we solved solution preferentially bound by RHA. Evidence...
Significance Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that widely distributed bacteria, archaea, and their viruses. DGRs use a reverse transcriptase (RT)-mediated mechanism to diversify protein-encoding genes facilitate adaptation of hosts changing environments. Here, we demonstrate the Bordetella phage DGR-encoded RT uses 3′-OH nicked template RNA initiate transcription, during which random nucleotides incorporated when adenine residues copied...
Recombinant human bone morphogenetic proteins (rhBMPs) can stimulate formation and growth in the treatment of spinal fusions nonunions.However, it is still unclear whether rhBMPs function prevention intervertebral disc degeneration (IDD).Here, we discovered that BMP levels were decreased IDD patients, which impaired BMP/Smad (Mothers against decapentaplegic homologs) signaling.Conducting a microarray assay Smad4-knockdown cells, found expression PUMA (p53-upregulated modulator apoptosis) was...
The HIV-1 capsid protein (CA) assumes distinct structural forms during replication, each presenting unique, solvent-accessible surfaces that facilitate multifaceted functions and host factor interactions. However, functional contributions of individual CA structures remain unclear, as evaluation presents several technical challenges. To address this knowledge gap, we identified CA-targeting aptamers with different specificities, which emerged through a branched SELEX approach using an...
The field of therapeutic peptides is experiencing a surge, fueled by their advantageous features. These include predictable metabolism, enhanced safety profile, high selectivity, and reduced off-target effects compared with small-molecule drugs. Despite progress in addressing limitations associated peptide drugs, significant bottleneck remains: the absence large-scale silico screening method for given protein target structure. Such methods have proven invaluable accelerating drug discovery....