A5055037655- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Underwater Vehicles and Communication Systems
- Robotic Path Planning Algorithms
- Adaptive Control of Nonlinear Systems
- Influenza Virus Research Studies
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Biosensors and Analytical Detection
- DNA Repair Mechanisms
- Cancer therapeutics and mechanisms
- Telomeres, Telomerase, and Senescence
- PARP inhibition in cancer therapy
- Respiratory viral infections research
- Conducting polymers and applications
- Microplastics and Plastic Pollution
- Cell death mechanisms and regulation
- Viral gastroenteritis research and epidemiology
- Innovative Microfluidic and Catalytic Techniques Innovation
Hunan University
2023-2024
Sun Yat-sen University
2020-2023
Institute of Zoology
2011-2021
Chinese Academy of Sciences
2009-2021
University of Chinese Academy of Sciences
2017
Wuhan University
2009-2011
Harbin Engineering University
2007-2008
Telomere G-quadruplex is emerging as a promising anti-cancer target due to its inhibition telomerase, an enzyme expressed in more than 85% tumors. Telomerase-mediated telomere extension and some other reactions require free 3′ end single-stranded form. formation near the of DNA can leave tail various sizes. How these terminal structures affect at not clear. In this work, we studied size-dependence by either telomerase or alternative lengthening (ALT) mechanism well unwinding. We show that...
Large numbers of guanine-rich sequences with potential to form G-quadruplexes have been identified in genomes various organisms. Such are constrained at both ends by long DNA duplex a complementary strand close proximity compete for formation. G-quadruplex/duplex competition double-stranded has rarely studied. In this work, we used DMS footprinting and gel electrophoresis study G-quadruplex formation derived from human genome under dilute molecular crowding condition created PEG. was...
Abstract G-quadruplex (G4) structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes serve as important drug targets. The genome-wide detection of G4s living cells is for exploring the functional role but has not yet been achieved due to lack a suitable G4 probe. Here we report an artificial 6.7 kDa probe (G4P) protein that binds with high affinity specificity. We used it capture human, mouse, chicken ChIP-Seq technique, yielding...
G-quadruplex formation in genomic DNA is considered to regulate transcription. Previous investigations almost exclusively focused on intramolecular G-quadruplexes formed by carrying four or more G-tracts, and structure has rarely been studied physiologically relevant processes. Here, we report an entirely neglected, but actually much prevalent form of G-quadruplexes, DNA:RNA hybrid (HQ) that forms HQ requires as few two G-tracts instead a non-template strand. Potential sequences (PHQS) are...
Significance Guanine-rich nucleic acids fold into a four-stranded structure named G-quadruplex that has implications in essential cellular processes, pharmaceutical applications, and nanodevices. We found unique type of contains G-vacancy is stabilized by guanine derivatives such as te physiological concentration GTP fill-in at the base. In response to changes derivatives, this able manipulate tracking activity protein on DNA exemplified polymerase-catalyzed synthesis. Because are natural...
We recently reported that a DNA:RNA hybrid G-quadruplex (HQ) forms during transcription of DNA bears two or more tandem guanine tracts (G-tract) on the nontemplate strand. Putative HQ-forming sequences are enriched in nearby 1000 nt region right downstream start sites strand warm-blooded animals, and HQ regulates under both vitro vivo conditions. Therefore, knowledge mechanism formation is important for understanding biological function as well manipulating gene expression by targeting HQ....
Significance Our work reveals the genome-wide prevalence of G4 structural variations (G4Vs) associated with single-nucleotide (SNVs) in human genome and how such G4Vs interact gene-regulatory elements subsequently affect activities genes accommodating G4Vs. The are enriched around transcription start sites, implying their potential involvement gene expression. Because structures participate essential physiological pathological processes, should make crucial contributions to genotype...
Telomere DNA in human cells shortens during each round of replication. In cancer cells, telomere shortening is compensated by telomerase or the alternative lengthening (ALT) mechanism to maintain cell division potential. The G-rich strand can fold into a G-quadruplex structure and disrupt these two processes. Therefore, stabilization chemical ligands emerging as promising anticancer strategy. So far, vitro studies on such are exclusively carried out dilute solutions. However, intracellular...
G-quadruplexes, four-stranded structures formed by Guanine-rich nucleic acids, are implicated in many physiological and pathological processes. G-quadruplex-forming sequences abundant genomic DNA, G-quadruplexes have recently been shown to exist the genome of mammalian cells. However, how genomes remains largely unclear. Here, we show that G-quadruplex formation can be remotely induced downstream transcription events thousands base pairs away. The alter protein recognition cause termination...
Recently, we reported the co-transcriptional formation of DNA:RNA hybrid G-quadruplex (HQ) structure by non-template DNA strand and nascent RNA transcript, which in turn modulates transcription under both vitro vivo conditions. Here present bioinformatic analysis on putative HQ-forming sequences (PHQS) genomes eukaryotic organisms. Starting from amphibian, PHQS motifs are concentrated immediate 1000-nt region downstream start sites, implying their potential role regulation. Moreover,...
Human mitochondrial DNA contains a distinctive guanine-rich motif denoted conserved sequence block II (CSB II) that stops RNA transcription, producing prematurely terminated transcripts to prime replication. Recently, we reported general phenomenon DNA:RNA hybrid G-quadruplexes (HQs) readily form during transcription when the non-template strand is and such HQs in turn regulate transcription. In this work, show of leads formation stable HQ or alternatively an unstable intramolecular...
Abstract Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal in human cells. However, the reason its retention remained unclear. In this study, we discovered close association between DNA, specifically linked to presence of G-quadruplex (G4) structures. G4 structures, formed...
Developing broad-spectrum influenza vaccines is crucial for control and potential pandemic preparedness. Here, we reported a novel vaccine design utilizing circular RNA (circRNA) as delivery platform multi-subtype neuraminidases (NA) (influenza A N1, N2, B Victoria lineage NA) immunogens. Individual NA circRNA lipid nanoparticles (LNP) elicited robust NA-specific antibody responses with neuraminidase inhibition activity (NAI), preventing the virus from egressing infecting neighboring cells....
Abstract DNA with four guanine tracts can fold into G‐quadruplexes that are targets of transcription regulation. We recently found hybrid DNA:RNA (HQs) form during in vitro transcription. However, it is unclear whether they cells. Evidence presented supporting their formation plasmids bacterial The the HQs indicated by a unique pattern prematurely terminated transcripts under two conditions where RNA do or not participate G‐quadruplex assembly and further supported number chemical...
Stabilization of G-quadruplexes (G4s) formed in guanine-rich (G-rich) nucleic acids by small-molecule ligands has been extensively explored as a therapeutic approach for diseases such cancer. Finding with sufficient affinity and specificity toward G4s remains challenge, many reported seemed to compromise between the two features. To cope this we focused on targeting particular type G4s, i.e., G-vacancy-bearing (GVBQs), taking structure complementation strategy enhance both selectivity. In...
A matter of speed: When allowed to fold in a K+/poly(ethylene glycol) solution, the guanine (G)-rich strand vertebrate telomere DNA forms parallel/antiparallel G-quadruplex, which is (3+1) hybrid, within microseconds before slowly transforming into parallel one hours (see picture). Thus, conformation that G-quadruplex initially adopts under physiological conditions may not be it at equilibrium state. Detailed facts importance specialist readers are published as ”Supporting Information”. Such...
Transcription induces formation of intramolecular G-quadruplex structures at the upstream region a DNA duplex by an upward transmission negative supercoiling through DNA. Currently regulation such remains unclear. Using plasmid as model, we demonstrate that while it is dynamic generated moving RNA polymerase triggers G-quadruplex, constitutional superhelicity determines potential and range constraining propagation supercoiling. maximal in negatively supercoiled nearly abolished relaxed...
Abstract G‐quadruplexes are implicated in important cellular processes. Previous studies mostly focused on intramolecular of three or more G‐quartets. Those composed two G‐quartets were only shown to form single‐stranded oligonucleotides. On the basis electrophoresis, DMS footprinting, fluorescence labeling, and photo‐cross‐linking, we detected formation DNA:RNA hybrid (HQs) during transcription DNA duplexes. These HQs have a lifetime minute scale stabilized by stabilizing ligand. They far...
EGFR tyrosine kinase inhibitors have made remarkable success in targeted cancer therapy. However, therapeutic resistance inevitably occurred and EGFR-targeting therapy has been demonstrated to limited efficacy or utility glioblastoma, colorectal cancer, hepatocellular carcinoma. Therefore, there is a high demand for the development of new targets inhibit signaling. Herein, we found that oncogene proximal promoter sequence forms unique type snap-back loop containing G-quadruplex (G4), which...
The widespread of G-quadruplex-forming sequences in genomic DNA and their role regulating gene expression has made G-quadruplex structures attractive therapeutic targets against a variety diseases, such as cancer. Information on the structure G-quadruplexes is crucial for understanding physiological roles designing effective drugs them. Resolving G-quadruplexes, however, remains challenge especially those double-stranded DNA. In this work, we developed photocleavage footprinting technique to...
A guanine-vacancy-bearing G-quadruplex (GVBQ) interacts with guanine and derivatives by a structural complementation to form more stable intact G-quadruplex. Sensors using GVBQs are devised detect other nucleobases, their derived from structurally similar compounds. strict requirement of Hoogsteen hydrogen bonds between the GVBQ analyte in confers exceptional selectivity on analyte. As such, subtle modifications analytes affecting even single bond can preclude recognition. In principle,...
DNA supercoiling is an important regulator of gene activity. The transmission transcription-generated wave along a helix provides way for being transcribed to communicate with and regulate its neighboring genes. Currently, the dynamic behavior remains unclear owing lack suitable tool detecting dynamics transmission. In this work, we established torsion sensor that quantitatively monitors in real time DNA. Using sensor, studied transcriptionally generated negative linear multi-way duplexes....
Abstract A significant number of sequences in the human genome form noncanonical G-quadruplexes (G4s) with bulges or a guanine vacancy. Here, we systematically characterized mechanical stability parallel-stranded G4s one to seven nucleotides bulge at various positions. Our results show that G4-forming multiple conformations, including fully-folded G4 high (unfolding forces > 40 pN), partially-folded intermediates < pN). The folding probability and folded populations strongly...
RNA G-quadruplex formation in a defined sequence living bacterial cells is detected by bimolecular fluorescence complementation with and structure specificity.