A5087307890- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Cancer-related molecular mechanisms research
- Pancreatitis Pathology and Treatment
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Liver Disease Diagnosis and Treatment
- Antibiotic Resistance in Bacteria
- Diabetes and associated disorders
- Peptidase Inhibition and Analysis
- Bacterial Genetics and Biotechnology
- Genomics, phytochemicals, and oxidative stress
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Cholesterol and Lipid Metabolism
- Caveolin-1 and cellular processes
- Cancer, Stress, Anesthesia, and Immune Response
- Phytochemicals and Antioxidant Activities
- Histone Deacetylase Inhibitors Research
- Erythrocyte Function and Pathophysiology
- Cancer Mechanisms and Therapy
- Biochemical and Molecular Research
Xi'an Jiaotong University
2024-2025
First Affiliated Hospital of Xi'an Jiaotong University
2021-2025
Chinese Academy of Medical Sciences & Peking Union Medical College
2024-2025
Peking Union Medical College Hospital
2024-2025
Qingdao University
2024
Affiliated Hospital of Qingdao University
2024
ShanghaiTech University
2020-2024
University of Chinese Academy of Sciences
2015-2021
Center for Excellence in Molecular Cell Science
2012-2021
Chinese Academy of Sciences
2007-2017
5-methylcytosine (m5C) modifications of RNA are ubiquitous in nature and play important roles many biological processes such as protein translational regulation, processing stress response. Aberrant expressions RNA:m5C methyltransferases closely associated with various human diseases including cancers. However, no structural information for RNA-bound methyltransferase was available until now, hindering elucidation the catalytic mechanism behind methylation. Here, we have solved structures...
Introduction: NBP is a compound isolated from celery seeds, which was approved by the National Medical Products Administration in 2002 for clinical treatment of ischemic stroke. However, brain ischemia/reperfusion (I/R) injury, related research on mitochondrial dynamics and its mechanism action still need to be further studied. The aim this study assess cerebral pathology stroke vivo , with specific focus molecular mechanisms how promotes fusion. Methods: Male C57BL/6 mice were utilized...
MitoNEET was identified as an outer mitochondrial membrane protein that can potentially bind the anti-diabetes drug pioglitazone. The crystal structure of cytoplasmic mitoNEET (residues 33-108) is determined in this study. presents a novel fold and contains [2Fe-2S] cluster-binding domain. cluster coordinated to by Cys-72, Cys-74, Cys-83, His-87 residues. This coordination also compared with traditional four cysteines or two histidines. forms homodimers solution crystal. dimerization mainly...
Streptococcus pneumoniae causes bacterial pneumonia with high mortality and morbidity. The emergency of multidrug-resistant bacteria threatens the treatment disease. Leucyl-tRNA synthetase (LeuRS) plays an essential role in cellular translation is attractive drug target for antimicrobial development. Here we report compound ZCL039, a benzoxaborole-based derivative AN2690, as potent anti-pneumococcal agent that inhibits S. LeuRS (SpLeuRS) activity. We show using kinetic, biochemical analyses...
The apicomplexan parasites Cryptosporidium and Toxoplasma are serious threats to human health. Cryptosporidiosis is a severe diarrheal disease in malnourished children immunocompromised individuals, with the only FDA-approved drug treatment currently being nitazoxanide. existing therapies for toxoplasmosis, an important pathology individuals pregnant women, also have limitations. With aim of developing alternative therapeutic options address these health problems, we tested number...
Post-transcriptional modifications affect tRNA biology and are closely associated with human diseases. However, progress on the functional analysis of in metazoans has been slow because difficulty identifying modifying enzymes. For example, biogenesis function prevalent N2-methylguanosine (m2G) at sixth position tRNAs eukaryotes long remained enigmatic. Herein, using a reverse genetics approach coupled RNA-mass spectrometry, we identified that THUMP domain-containing protein 3 (THUMPD3) is...
Abstract The mechanisms by which the relatively conserved spliceosome manages enormously large number of splicing events that occur in humans (∼200 000 versus ∼300 yeast) are poorly understood. Here, we show deposition one RNA modification-N2-methylguanosine (m2G) on G72 U6 snRNA (the catalytic center spliceosome) promotes efficient pre-mRNA activity human cells. This modification was identified to be among vertebrates. Further, THUMPD2 demonstrated as methyltransferase responsible for m2G72...
Article18 June 2020Open Access Source DataTransparent process Intellectual disability-associated gene ftsj1 is responsible for 2′-O-methylation of specific tRNAs Jing Li State Key Laboratory Molecular Biology, CAS Center Excellence in Cell Science, Shanghai Institute Biochemistry and Chinese Academy Sciences, University Shanghai, China School Life Science Technology, ShanghaiTech University, Search more papers by this author Yan-Nan Wang Advanced Immunochemical Studies, Bei-Si Xu...
Pancreatic cancer is a lethal disease with an insidious onset, and little known about its early molecular events. Here, we found that the sterol regulatory element-binding protein 1 (SREBP1) expression gradually upregulated during initiation of pancreatic cancer. Through in vitro 3D culture acinar cells experiments LSL-KrasG12D/+;Pdx1-Cre (KC) mice, pharmacological inhibition SREBP1 suppressed tumorigenesis. In vitro, either knockdown or tumor proliferation but overexpression promoted...
Unlike other transfer RNAs (tRNA)-modifying enzymes from the SPOUT methyltransferase superfamily, tRNA (Um34/Cm34) TrmL lacks usual extension domain for binding and consists only of a domain. Both catalytic recognition mechanisms this enzyme remain elusive. By using tRNAs purified an Escherichia coli strain with gene deleted, we found that can independently catalyze methyl S-adenosyl-L-methionine to isoacceptors without involvement tRNA-binding proteins. We have solved crystal structures in...
Human NOL1/NOP2/Sun RNA methyltransferase family member 6 (hNSun6) generates 5-methylcytosine (m5C) at C72 of four specific tRNAs, and its homologs are present only in higher eukaryotes hyperthermophilic archaea. Archaeal NSun6 possess conserved catalytic residues, but have distinct differences their recognition motifs from eukaryotic NSun6s. Until now, the biochemical properties functions archaeal were unknown. In archaeon Pyrococcus horikoshii OT3, gene encoding homolog is PH1991. We...
Post-transcriptional modifications bring chemical diversity to tRNAs, especially at positions 34 and 37 of the anticodon stem-loop (ASL). TrmL is prokaryotic methyltransferase that catalyzes transfer methyl group from S-adenosyl-L-methionine wobble base tRNALeuCAA tRNALeuUAA isoacceptors. This Cm34/Um34 modification affects codon-anticodon interactions essential for translational fidelity. TrmL-catalyzed 2′-O-methylation requires its homodimerization; however, understanding tRNA recognition...
Dnmt2, a member of the DNA methyltransferase superfamily, catalyzes formation 5-methylcytosine at position 38 in anticodon loop tRNAs. Dnmt2 regulates many cellular biological processes, especially production tRNA-derived fragments and intergenerational transmission paternal metabolic disorders to offspring. Moreover, is closely related human cancers. The tRNA substrates mammalian Dnmt2s are mainly detected using bisulfite sequencing; however, we lack supporting biochemical data concerning...
Low responsiveness to chemotherapy is an important cause of poor prognosis in pancreatic cancer. Smoking a high-risk factor for cancer and resistance gemcitabine; however, the underlying mechanisms remain unclear. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) main metabolite tobacco burning has been shown be associated with development chemoresistance. However, cancer, its mechanism remains poorly understood. In this study, we found that NNK promoted stemness gemcitabine cell lines....
5-methylcytosine RNA modifications are driven by NSUN methyltransferases. Although variants in NSUN2 and NSUN3 were associated with neurodevelopmental diseases, the physiological role of NSUN6 on transfer RNAs messenger remained elusive.We combined exome sequencing consanguineous families functional characterization to identify a new disorder gene.We identified 3 unrelated deleterious homozygous NSUN6. Two these predicted be loss-of-function. One maps first exon is lead absence via...