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Crystal structure of Cas1 in complex with branched DNA

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Science China(Life Sciences) 2020年第4期63卷 516-528页

作者： Jing Yang Jiazhi Li Jiuyu Wang Gang Sheng Min Wang Hongtu Zhao Yanhua Yang Yanli Wang Institute of Life Sciences Jiangsu UniversityZhenjiang 212013China Key Laboratory of rna Biology CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China

Cas1 is a key component of the CRISPR adaptation complex,which captures and integrates foreign DNA into the CRISPR array,resulting in the generation of new *** have determined crystal structures of Thermus thermophilus Cas1 involved in new spacer acquisition both in complex with branched DNA and in the free ***1 forms an asymmetric dimer without ***,two asymmetrical dimers bound to two branched DNAs result in the formation of a DNA-mediated tetramer,dimer of structurally asymmetrical dimers,in which the two subunits markedly present different *** the DNA binding complex,the N-terminal domain adopts different orientations with respect to the C-terminal domain in the two monomers that form the *** binding triggers a conformational change in the loop 164–177 *** loop is also involved in the 3′fork arm and 5′fork arm strand recognition in monomer A and B,*** study provides important insights into the molecular mechanism of new spacer adaptation.

关键词： CRISPR Cas protein Cas1 adaptation DNA integration structure protein-DNA complex

脑膜瘤端粒酶活性检测及其rna和hTERT的表达

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中国神经精神疾病杂志 2001年第5期27卷 348-351页

作者：尤永平浦佩玉彭琼夏之柏黄强王春燕王广秀天津医科大学总医院神经外科脑肿瘤室天津300052 人端粒酶rna 人端粒酶逆转录酶脑膜瘤

目的　研究脑膜瘤的端粒酶活性及其ＲＮＡ和人端粒酶逆转录酶（ｈＴＥＲＴ）的表达，为临床诊断和治疗开拓新思路。方法　改良ＴＲＡＰ法及ＲＴ－ＰＣＲ检测４０例脑膜瘤的端粒酶活性及其ＲＮＡ和ｈＴＥＲＴ表达。结果　脑膜瘤端粒酶阳... 详细信息

目的　研究脑膜瘤的端粒酶活性及其ＲＮＡ和人端粒酶逆转录酶（ｈＴＥＲＴ）的表达，为临床诊断和治疗开拓新思路。方法　改良ＴＲＡＰ法及ＲＴ－ＰＣＲ检测４０例脑膜瘤的端粒酶活性及其ＲＮＡ和ｈＴＥＲＴ表达。结果　脑膜瘤端粒酶阳性率为４２．５％，ｈＴＥＲＴ阳性率５２．５％，两者都随肿瘤恶性度增加而升高；人端粒酶ＲＮＡ（ｈＴＲ）广泛存在于脑膜瘤和正常脑组织中。结论　端粒酶活性及ｈＴＥＲＴ和脑膜瘤恶性程度有关，有助于临床诊断，可能成为新治疗靶点；ｈＴＥＲＴ是端粒酶活性调节的关键。

关键词：端粒酶活性人端粒酶rna 人端粒酶逆转录酶脑膜瘤

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纳米酶的抗菌机理与应用

生物化学与生物物理进展 2018年第2期45卷 118-128页

作者：唐燕仇智月许卓斌高利增扬州大学医学院转化医学研究院江苏省非编码rna基础与临床转化重点实验室

细菌耐药性和抗生素滥用是一个世界性难题,需要开发新型抗菌剂,既能够高效杀菌,又能避免耐药性问题并具有较好的生物和环境相容性.纳米酶具有调控ROS自由基的能力,可以高效杀死多种革兰氏阳性和阴性致病菌以及顽固性生物膜;同时纳米酶... 详细信息

细菌耐药性和抗生素滥用是一个世界性难题,需要开发新型抗菌剂,既能够高效杀菌,又能避免耐药性问题并具有较好的生物和环境相容性.纳米酶具有调控ROS自由基的能力,可以高效杀死多种革兰氏阳性和阴性致病菌以及顽固性生物膜;同时纳米酶具有较好的稳定性、生物相容性、可回收再利用等优点,在促进伤口愈合、龋齿防治和环境防污方面具有重要的应用前景.

关键词：纳米酶 ROS 细菌耐药性生物膜

Virus-Induced Flowering In Dicot And Monocot Crops

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Virus-Induced Flowering In Dicot And Monocot Crops

Role of Long Non-coding rnas in Reprogramming to Induced Pluripotency

第三届全国植物开花·衰老与采后生物学大会

作者： Yiguo Hong Research Centre for Plant rna Signaling College of Life and Environmental S ciencesHangzhou Normal University

Virus-induced flowering（VIF） assays exploit rna or DNA viruses to express flowering time genes such as Flowering Locus T（FT） to induce flowering in plants1,2. Such plant virus-based techniques have recently attracted widespread attention for their fundamental and applied uses in flowering physiology and in accelerating breeding in dicot crops and woody fruit-trees. However, the insight into VIF, its potential as a powerful tool for dissecting florigenic proteins as well as its establishment in monocot crops remained to be elucidated. During my presentation, I will briefly explain different forms of virus-based technology for plant functional genomics, then move onto describing the mechanism and further applications of VIF in the short-day Nicotiana tabacum cultivar Maryland Mammoth, a dicot plant3. I will also present our latest work onextending this technology for the first time to proso millet, a monocot grass and wheat, a cereal crop4. These will lead to conclude that VIF represents a simple and efficient system to identify individual amino acids that are essential for FT-mediated floral induction and to test the ability of mono-and dicotyledonous FT genes and FT fusion proteins to induce flowering. VIF is also applicable to many economically important monocotyledonous food and biofuel crops.

关键词： Virus-Induced Dicot Monocot Crops

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Genomics, Proteomics & Bioinformatics 2020年第1期18卷 16-25页

作者： Shahzina Kanwal Xiangpeng Guo Carl Ward Giacomo Volpe Baoming Qin Miguel A.Esteban Xichen Bao Joint School of Life Sciences Guangzhou Medical University and Guangzhou Institutes of Biomedicine and HealthGuangzhou 511436China Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Laboratory of rna Chromatinand Human DiseaseGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Guangzhou Regenerative Medicine and Health Guangdong Laboratory(GRMH-GDL) Guangzhou 510005China Laboratory of Metabolism and Cell Fate Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Institute for Stem Cells and Regeneration Chinese Academy of SciencesBeijing 100101China Laboratory of rna Molecular Biology Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China

The generation of induced pluripotent stem cells through somatic cell reprogramming requires a global reorganization of cellular *** reorganization occurs in a multi-phased manner and involves a gradual revision of both the epigenome and *** studies have shown that the large-scale transcriptional changes observed during reprogramming also apply to long noncoding rnas(lncR NAs),a type of traditionally neglected rna species that are increasingly viewed as critical regulators of cellular *** understanding of lncR NAs in reprogramming may not only help to improve this process but also have implications for studying cell plasticity in other contexts,such as development,aging,and *** this review,we summarize the current progress made in profiling and analyzing the role of lncR NAs in various phases of somatic cell reprogramming,with emphasis on the re-establishment of the pluripotency gene network and X chromosome reactivation.

关键词： Mesenchymal-to-epithelial transition X chromosome reactivation Apoptosis Proliferation

CRISPR-Cas Mediated Cleavage of Invading rnas

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CRISPR-Cas Mediated Cleavage of Invading RNAs

All types of base conversions allowed by base editors

中国生物化学与分子生物学会2019年全国学术会议暨学会成立四十周年

作者： Liu Liang Li Jiazhi Wang Jiuyu Ma Jun Wang Min Li Xueyan Wang Yanli Key Laboratory of rna Biology Institute of Biophysics Chinese Academy of Sciences University of Chinese Academy of Sciences

Bacteria and archaea are protected against invading nucleic acids from phages and plasmids because of CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)-Cas(CRISPR associated proteins)systems,which are rna-guided prokaryotic adaptive immune ***-Cas systems are found in nearly half of all bacteria studied so far,as well as in the majority of ***-Cas systems

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Science China(Life Sciences) 2024年第2期67卷 431-433页

作者： Shun-Qing Liang Wen Xue rna Therapeutics Institute UMass Chan Medical SchoolWorcester 01655USA Department of Molecular Cell and Cancer BiologyUMass Chan Medical SchoolWorcester 01655USA Department of Molecular Medicine UMass Chan Medical SchoolWorcester 01655USA Li Weibo Institute for Rare Diseases Research UMass Chan Medical SchoolWorcester 01655USA

Base editors(BEs) hold great promise as tools for introducing single-base-pair changes in both basic research and therapeutic applications(Rees and Liu,2018).Base editors are composed of a Cas9 nickase fused to a DNA-modifying enzyme,which chemically modifies nucleobases within a specific targeting window near the Cas9-binding site.

关键词： base bases allowed

Visualized and cascade-enhanced gene silencing by smart DNAzyme-graphene nanocomplex

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Nano Research 2020年第8期13卷 2165-2174页

作者： Lingjie Ren Xiaoxia Chen Chang Feng Lei Ding Xiaomin Liu Tianshu Chen Fan Zhang Yanli Li Zhongliang Ma Bo Tian Xiaoli Zhu Center for Molecular Recognition and Biosensing School of Life SciencesShanghai UniversityShanghai200444China School of Medical Shanghai UniversityShanghai200444China Lab for Noncoding rna and Cancer School of Life SciencesShanghai UniversityShanghai200444China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200032China

BCL-2 gene as well as its products is recognized as a promising target for the molecular targeted therapy of ***,due to certain defense measures of tumor cells,the therapeutic effect based on the gene silencing of BCL-2 is greatly *** we fabricate a smart response nucleic acid therapeutic that could silence the gene effectively through a dual-targeted and cascade-enhanced *** brief,nano-graphene oxide(GO),working as a nano-carrier,is loaded with a well-designed DNAzyme,which can target and silence the BCL-2 ***,upon binding with the BCL-2 mrna,the enzymatic activity of the DNAzyme can be initiated,cutting a substrate oligonucleotide to produce an anti-nucleolin aptamer ***,a nucleolar phosphoprotein,is known as a stabilizer of BCL-2 *** binding and inactivating the nucleolin,AS1411 can destabilize BCL-2 *** this means of simultaneously targeting mrna and its stabilizer in an integrated system,effective silencing of the BCL-2 gene of tumor cells is achieved at both the cellular and in vivo *** being dosed with this nucleic acid therapeutic and without any chemotherapeutics,apoptosis of tumor cells at the cellular level and apparent shrinkage of tumors in vivo are *** labeling a molecular beacon on the substrate of DNAzyme,visualization of the enzymatic activity as well as the tumor in vivo can be also *** work presents a pure bio-therapeutic strategy that has positive implications for enhancing tumor treatment and avoiding side effects of chemotherapeutics.

关键词： BCL-2 gene gene silencing DNAzyme graphene oxide AS1411

Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance

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Science China(Life Sciences) 2024年第1期67卷 19-40页

作者： Jing Cai Xiaoding Xu Phei Er Saw Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Nanhai Translational Innovation Center of Precision Immunology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityFoshan 528200China

A potential reason for the failure of tumor therapies is treatment *** to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and *** major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,*** studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell *** ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor ***,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback ***,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor *** also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.

关键词： ferroptosis cancer therapy therapy resistance nanoinducers