A5108239310- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- Genomics and Chromatin Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Advanced Electron Microscopy Techniques and Applications
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- Electron and X-Ray Spectroscopy Techniques
- Protein Structure and Dynamics
- Viral Infections and Outbreaks Research
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Generative Adversarial Networks and Image Synthesis
- 3D Shape Modeling and Analysis
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
University of Chinese Academy of Sciences
2016-2025
Chinese Academy of Sciences
2016-2025
Institute of Biophysics
2015-2025
Wuhan Textile University
2020-2024
First Hospital of Shijiazhuang
2024
Jiangsu University of Science and Technology
2023-2024
Chengdu University of Information Technology
2023
Zhejiang A & F University
2023
Shanghai Jiao Tong University
2010-2022
Czech Academy of Sciences, Institute of Biophysics
2022
Human antibody 2G12 neutralizes a broad range of human immunodeficiency virus type 1 (HIV-1) isolates by binding an unusually dense cluster carbohydrate moieties on the "silent" face gp120 envelope glycoprotein. Crystal structures Fab and its complexes with disaccharide Manalpha1-2Man oligosaccharide Man9GlcNAc2 revealed that two Fabs assemble into interlocked VH domain-swapped dimer. Further biochemical, biophysical, mutagenesis data strongly support Fab-dimerized as prevalent form...
The hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Here, we report the 11-angstrom-resolution cryogenic electron microscopy (cryo-EM) structures 30-nanometer fibers reconstituted presence linker histone H1 with different nucleosome repeat lengths. show H1-dependent left-handed twist repeating tetranucleosomal structural units, within which four nucleosomes zigzag back forth straight DNA. asymmetric...
Recurrent mutations in the spliceosome are observed several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, most frequently mutated component of cancer, is involved recognition branch point sequence (BPS) during selection 3' splice site (ss) RNA splicing. Here, we report that common tumor-specific splicing aberrations induced by SF3B1 establish aberrant ss as frequent defect. Strikingly, mutant utilizes a BPS differs from used wild-type requires...
We used electron tomography to directly visualize trilobed presumptive envelope (env) glycoprotein structures on the surface of negatively stained HIV type 1 (HIV-1) and simian immunodeficiency virus (SIV) virions. Wild–type HIV-1 SIV virions had an average 8–10 trimers per virion, consistent with predictions based biochemical evidence. Mutant SIVs, biochemically demonstrated contain high levels viral env proteins, averaged 70–79 virion in tomograms. These correlations strongly indicate that...
Hotspot mutations in splicing factor genes have been recently reported at high frequency hematological malignancies, suggesting the importance of RNA cancer. We analyzed whole-exome sequencing data across 33 tumor types The Cancer Genome Atlas (TCGA), and we identified 119 with significant non-silent mutation patterns, including over-representation, recurrent loss function (tumor suppressor-like), or hotspot profile (oncogene-like). Furthermore, analysis revealed altered events associated...
Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing by their ability to recognize functional gp120/gp41 envelope glycoprotein (Env) trimers. The antibody responses induced natural HIV-1 infection or vaccine candidates tested date consist largely of antibodies. One might have expected a more vigorous response, particularly against particles that bear recent surprising observation can specifically capture may provide clue...
The histone variants H3.3 and H2A.Z have recently emerged as two of the most important features in transcriptional regulation, molecular mechanism which still remains poorly understood. In this study, we investigated regulation on chromatin dynamics during activation. Our vitro biophysical biochemical investigation showed that promoted compaction repressed activity. Surprisingly, with only four to five amino acid differences from canonical H3, greatly impaired higher-ordered folding gene...
Eliciting broad tier 2 neutralizing antibodies (nAbs) is a major goal of HIV-1 vaccine research. Here we investigated the ability native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 8 rabbits immunized with virus-like particles (VLPs) expressing (trimer VLP sera) and 1 20 DNA native trimer, followed by protein boost (DNA trimer sera). All 3 sera neutralized via quaternary epitopes exploited natural gaps glycan defenses second conserved region...
Abstract Pladienolide, herboxidiene and spliceostatin have been identified as splicing modulators that target SF3B1 in the SF3b subcomplex. Here we report PHF5A, another component of this subcomplex, is also targeted by these compounds. Mutations PHF5A-Y36, SF3B1-K1071, SF3B1-R1074 SF3B1-V1078 confer resistance to modulators, suggesting a common interaction site. RNA-seq analysis reveals PHF5A-Y36C has minimal effect on basal but inhibits global action modulators. Moreover, alters...
The role of dysregulation mRNA alternative splicing (AS) in the development and progression solid tumors remains to be defined. Here we describe first comprehensive AS landscape spectrum human prostate cancer (PCa) evolution. We find that severity correlates with disease establish intron retention as a hallmark PCa stemness aggressiveness. Systematic interrogation 274 splicing-regulatory genes (SRGs) uncovers prevalent genomic copy number variations (CNVs), leading mis-expression ~68% SRGs...
Somatic mutations in spliceosome proteins lead to dysregulated RNA splicing and are observed a variety of cancers. These genetic aberrations may offer potential intervention point for targeted therapeutics. SF3B1, part the U2 small nuclear RNP (snRNP), is by modulators, including E7107, first enter clinical trials, and, more recently, H3B-8800. Modulating represents first-in-class opportunity drug discovery, elucidating structural basis mode action opens up new possibilities structure-based...
ABSTRACT We describe the further properties of a protein, designated SOS gp140, wherein association gp120 and gp41 subunits human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is stabilized by an intersubunit disulfide bond. HIV-1 JR-FL proteolytically uncleaved gp140 (gp140 UNC ), were expressed in stably transfected Chinese hamster ovary cells analyzed for antigenic structural before after purification. Compared with , reacted more strongly surface plasmon resonance...
The envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the major target neutralizing antibody responses and likely to be a critical component an effective vaccine against AIDS. Although monomeric HIV subunit vaccines (gp120) have induced high-titer antibodies laboratory-adapted HIV-1 strains, they failed induce diverse heterologous primary isolates. Most probably, reason for this failure that antigenic structure(s) these previously used immunogens does not mimic...
Rationale: Tumor metastasis is the main cause for cancer-related death. However, driving molecules of remain largely unknown. Here, we aim to identify long non-coding RNAs (lncRNAs) critical human hepatocellular carcinoma (HCC) metastasis. Methods: Microarrays were used screen a comprehensive set lncRNAs with differential expression profiles in sulfatide-treated cells. Mass spectrometry, protein arrays, and RNA pull-down experiments proteins that interacted lncRNA. Epigenetic analysis was...
Dysregulation of RNA splicing by spliceosome mutations or in cancer genes is increasingly recognized as a hallmark cancer. Small molecule modulators have been introduced into clinical trials to treat solid tumors leukemia bearing recurrent mutations. Nevertheless, further investigation the molecular mechanisms that may enlighten therapeutic strategies for highly desired. Here, using unbiased functional approaches, we report sensitivity modulation anti-apoptotic BCL2 family key mechanism...