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PTMD: A Database of Human Disease-associated Post-translational Modifications

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Genomics, Proteomics & Bioinformatics 2018年第4期16卷 244-251页

作者： Haodong Xu Yongbo Wang Shaofeng Lin Wankun Deng Di Peng Qinghua Cui Yu Xue Department of Bioinformatics & Systems Biology MOE Key Laboratory of Molecular Biophysics College of Life Science and Technology and the Collaborative Innovation Center for Biomedical Engineering Huazhong University of Science and Technology Department of Biomedical Informatics School of Basic Medical Sciences MOE Key Laboratory of Molecular Cardiovascular Sciences Center for Non-coding RNA Medicine Peking University

Various posttranslational modifications （PTMs） participate in nearly all aspects of biological processes by regulating protein functions, and aberrant states of PTMs are frequently implicated in human diseases. Therefore, an integral resource of PTM–disease associations （PDAs）would be a great help for both academic research and clinical use. In this work, we reported PTMD,a well-curated database containing PTMs that are associated with human diseases. We manually collected 1950 known PDAs in 749 proteins for 23 types of PTMs and 275 types of diseases from the literature. Database analyses show that phosphorylation has the largest number of disease associations, whereas neurologic diseases have the largest number of PTM associations. We classified all known PDAs into six classes according to the PTM status in diseases and demonstrated that the upregulation and presence of PTM events account for a predominant proportion of diseaseassociated PTM events. By reconstructing a disease–gene network, we observed that breast cancers have the largest number of associated PTMs and AKT1 has the largest number of PTMs connected to diseases. Finally, the PTMD database was developed with detailed annotations and can be a useful resource for further analyzing the relations between PTMs and human diseases. PTMD is freely accessible at http：//***.

关键词： Posttranslational modification Phosphorylation PTM-disease association Disease-gene network AKT1

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非编码rna与肝脏糖脂代谢调控

生理科学进展 2016年第3期47卷 194-202页

作者：杨卫利王君佩崔庆华杨吉春北京大学医学部基础医学院生理与病理生理系北京大学医学部非编码rna医学研究中心北京100191

随着经济的迅速发展、人们饮食习惯的改变和身体活动的减少,糖尿病成为了现代社会的非传染性的流行病,给家庭和社会造成了极大的危害和经济负担。其中以全身性胰岛素抵抗及胰岛功能衰竭为主要发病特征的2型糖尿病(type 2 diabetes,T2D)... 详细信息

随着经济的迅速发展、人们饮食习惯的改变和身体活动的减少,糖尿病成为了现代社会的非传染性的流行病,给家庭和社会造成了极大的危害和经济负担。其中以全身性胰岛素抵抗及胰岛功能衰竭为主要发病特征的2型糖尿病(type 2 diabetes,T2D)已在世界范围引起广泛关注。T2D的发生发展涉及许多组织及糖代谢的各个环节,遗传因素和环境因素共同引起的糖脂代谢通路任一环节的失调均可导致T2D的发生。近年来,包括microrna(mirna)及长非编码rna(Lncrna)在内的非编码rna(ncrna)的发现及其在人体生理和病理生理过程中的重要调控作用不断被揭示,为进一步了解T2D的发病机制注入了新理念和信息。mirnas及Lncrnas的表达具有组织特异性,其表达水平的异常通常与疾病相关。本文主要对mirnas和Lncrnas在肝脏糖脂代谢调控及T2D的发生发展中的作用及机制的最新研究进展作简要综述。

关键词： 2型糖尿病非编码rna mirna Lncrna 肝脏糖脂代谢

The Future Landscape and Framework of Precision Nutrition

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Engineering 2024年第11期42卷 15-25页

作者： Tianshu Han Wei Wei Wenbo Jiang Yiding Geng Zijie Liu Ruiming Yang Chenrun Jin Yating Lei Xinyi Sun Jiaxu Xu Juan Chen Changhao Sun Department of Nutrition and Food Hygiene the National Key DisciplineSchool of Public HealthHarbin Medical UniversityHarbin 150081China Key Laboratory of Precision Nutrition and Health Ministry of EducationHarbin Medical UniversityHarbin 150081China Key Laboratory of rna Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

The concept of precision nutrition was first proposed almost a decade *** research in precision nutrition primarily focuses on comprehending individualized variations in response to dietary intake,with little attention being given to other crucial aspects of precision ***,there is a dearth of comprehensive review studies that portray the landscape and framework of precision *** review commences by tracing the historical trajectory of nutritional science,with the aim of dissecting the challenges encountered in nutrition science within the new era of disease *** review also deconstructs the field of precision nutrition into four key components:the proposal of the theory for indi-vidualized nutritional requirement phenotypes;the establishment of precise methods for measuring dietary intake and evaluating nutritional status;the creation of multidimensional nutritional interven-tion strategies that address the aspects of what,how,and when to eat;and the construction of a pathway for the translation and integration of scientific research into healthcare practices,utilizing artificial intel-ligence and information *** these four components,this review further discusses prospective avenues that warrant exploration to achieve the objective of enhancing health through pre-cision nutrition.

关键词： Precision Nutrition Individualization nutrition Dietary measurement Dietary intervention Framework

Translation landscape of SARS-CoV-2 noncanonical subgenomic rnas

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Virologica Sinica 2022年第6期37卷 813-822页

作者： Kai Wu Dehe Wang Junhao Wang Yu Zhou State Key Laboratory of Virology College of Life SciencesWuhan UniversityWuhan430072China TaiKang Center for Life and Medical Sciences RNA InstituteWuhan UniversityWuhan430072China Institute for Advanced Studies Wuhan UniversityWuhan430072China Frontier Science Center for Immunology and Metabolism Wuhan UniversityWuhan430072China

The ongoing COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with a positive-stranded rna genome. Current proteomic studies of SARS-CoV-2 mainly focus on the proteins encoded by its genomic rna(grna) or canonical subgenomic rnas(sgrnas). Here, we systematically investigated the translation landscape of SARS-CoV-2, especially its noncanonical sgrnas. We first constructed a strict pipeline, named vipep, for identifying reliable peptides derived from rna viruses using rna-seq and mass spectrometry data. We applied vipep to analyze 24 sets of mass spectrometry data related to SARS-CoV-2infection. In addition to known canonical proteins, we identified many noncanonical sgrna-derived peptides,which stably increase after viral infection. Furthermore, we explored the potential functions of those proteins encoded by noncanonical sgrnas and found that they can bind to viral rnas and may have immunogenic activity. The generalized vipep pipeline is applicable to any rna viruses and these results have expanded the SARSCoV-2 translation map, providing new insights for understanding the functions of SARS-CoV-2 sgrnas.

关键词： SARS-CoV-2 Subgenomic rna(sgrna) Mass spectrometry Translation rna binding

CG hypermethylation of the bHLH39 promoter regulates its expression and Fe deficiency responses in tomato roots

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Horticulture Research 2023年第7期10卷 125-137页

作者： Huihui Zhu Guanghao Han Jiayi Wang Jiming Xu Yiguo Hong Li Huang Shaojian Zheng Jianli Yang Weiwei Chen State Key Laboratory of Plant Physiology and Biochemistry College of Life SciencesZhejiang UniversityHangzhou 310058China Research Centre for Plant rna Signaling College of Life and Environmental SciencesHangzhou Normal UniversityHangzhou 311121China Laboratory of Cell&Molecular Biology Institute of Vegetable ScienceZhejiang UniversityHangzhou 310058China

Iron(Fe)is an essential micronutrient for all organisms,including plants,whose limited bioavailability restricts plant growth,yield,and nutritional *** the transcriptional regulation of plant responses to Fe deficiency have been extensively studied,the contribution of epigenetic modulations,such as DNA methylation,remains poorly ***,we report that treatment with a DNA methylase inhibitor repressed Fe deficiency-induced responses in tomato(Solanum lycopersicum)roots,suggesting the importance of DNA methylation in regulating Fe deficiency *** changes in the DNA methylome in tomato roots responding to short-term(12 hours)and long-term(72 hours)Fe deficiency identified many differentially methylated regions(DMRs)and DMR-associated *** DMRs occurred at CHH sites under short-term Fe deficiency,whereas they were predominant at CG sites following long-term Fe ***,no correlation was detected between the changes in DNA methylation levels and the changes in transcript levels of the affected genes under either short-term or long-term ***,one exception was CG hypermethylation at the bHLH39 promoter,which was positively correlated with its transcriptional *** agreement,we detected lower CG methylation at the bHLH39 promoter and lower bHLH39 expression in MET1-rna interference lines compared with wild-type ***-induced gene silencing of bHLH39 and luciferase reporter assays revealed that bHLH39 is positively involved in the modulation of Fe ***,we propose that dynamic epigenetic DNA methylation in the CG context at the bHLH39 promoter is involved in its transcriptional regulation,thus contributing to the Fe deficiency response of tomato.

关键词： roots homeostasis treatment

SRSF1 plays a critical role in invariant natural killer T cell development and function

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Cellular & Molecular Immunology 2021年第11期18卷 2502-2515页

作者： Jingjing Liu Menghao You Yingpeng Yao Ce Ji Zhao Wang Fang Wang Di Wang Zhihong Qi Guotao Yu Zhen Sun Wenhui Guo Juanjuan Liu Shumin Li Yipeng Jin Tianyan Zhao Hai-Hui Xue Yuanchao Xue Shuyang Yu State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Agricultural UniversityBeijingChina Key Laboratory of rna Biology Institute of BiophysicsChinese Academy of SciencesBeijingChina Clinical Department College of Veterinary MedicineChina Agricultural UniversityBeijingChina Center for Discovery and Innovation Hackensack Meridian HealthNutleyNJUSA

Invariant natural killer T(iNKT)cells are highly conserved innate-like T lymphocytes that originate from CD4^(+)CD8^(+)double-positive(DP)***,we report that serine/arginine splicing factor 1(SRSF1)intrinsically regulates iNKT cell development by directly targeting Myb and balancing the abundance of short and long *** ablation of SRSF1 in DP cells led to a substantially diminished iNKT cell pool due to defects in proliferation,survival,and TCRα*** transition from stage 0 to stage 1 of iNKT cells was substantially blocked,and the iNKT2 subset was notably diminished in SRSF1-deficient ***1 deficiency resulted in aberrant expression of a series of regulators that are tightly correlated with iNKT cell development and iNKT2 differentiation,including Myb,PLZF,Gata3,ICOS,and *** particular,we found that SRSF1 directly binds and regulates pre-mrna alternative splicing of Myb and that the expression of the short isoform of Myb is substantially reduced in SRSF1-deficient DP and iNKT ***,ectopic expression of the Myb short isoform partially rectified the defects caused by ablation of ***,we confirmed that the SRSF1-deficient mice exhibited resistance to acute liver injury uponα-GalCer and Con A *** findings thus uncovered a previously unknown role of SRSF1 as an essential post-transcriptional regulator in iNKT cell development and functional differentiation,providing new clinical insights into iNKT-correlated disease.

关键词： Invariant natural killer T cell SRSF1 Development Function Alternative splicing

Key questions about the checkpoint blockade-are micrornas an answer?

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Cancer Biology & Medicine 2018年第2期15卷 103-115页

作者： Mihnea Dragomir Baoqing Chen Xiao Fu George A.Calin Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Research Center for Functional Genomics Biomedicine and Translational MedicineIuliu Hatieganu University of Medicine and Pharmacy Department of Surgery Fundeni Clinical HospitalCarol Davila University of Medicine and Pharmacy Center for rna Interference and Non-coding rnas The University of Texas MD Anderson Cancer Center

The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. Micro rnas are small rnas with no coding potential. By complementary pairing to the 3' untranslated region of messenger rna, micrornas exert posttranscriptional control of protein expression. A network of micrornas directly and indirectly controls the expression of checkpoint receptors and several micrornas can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the micrornas that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer:(1) imprecise therapeutic indication,(2) difficult response evaluation,(3) numerous immunologic adverse-events, and(4)the absence of response to immune therapy. Finally, we propose micrornas as possible solutions for these pitfalls. We consider that in the near future micrornas could become important therapeutic partners of the immune checkpoint therapy.

关键词： Microrna PD-1 PD-L1 CTLA-4 checkpoint inhibitors

Investigation on Viral Pathogens in <i>Vitis vinifera</i>from Four Production Bases in Hangzhou Vicinity of China by srnaseq and Molecular Validation

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American Journal of Plant Sciences 2021年第12期12卷 1791-1799页

作者： Hongmei Li Lingzhu Wei Jiang Wu Nongnong Shi Research Centre for Plant rna Signaling College of Life and Environmental Sciences Hangzhou Normal University Hangzhou China Research Centre for Plant rna Signaling College of Life and Environmental Sciences Hangzhou Normal University Hang-zhou China Institute of Horticulture Zhejiang Academy of Agricultural Sciences Hangzhou China

This is the first systematic investigation of viral pathogens in Vitis vinifera from Hangzhou vicinity of China. About 7 viruses and 5 viroids were annotated from four production bases “Dushicun”, “Wangjiayuan”, “Xiajiangcun”, and “Yangducun” covering 15 cultivars through srnaseq technique. At least 3 viruses—grapevine leaf roll-associated virus 3 (GLRaV-3), grapevine fleck virus (GFkV) and grapevine geminivirus A (GGVA), and 4 viroids—hop stunt viroid (HSVd), citrus viroid II (CVd-II), grapevine yellow speckle viroid 1 (GYSVd-1) and grapevine yellow speckle viroid 2 (GYSVd-2) infected all four bases. “Yangducun” base showed 11, the most infected pathogens. GYSVd-1 showed the highest accumulation in host of Wangjiayuan base. The main infected pathogens were verified by reverse-transcription polymerase chain reaction (RT-PCR) technique, the detected rate reached to 85% - 100%. The results provide an important basis for effective and precise detection of viral diseases in the area and for the virus-free cultivation in future.

关键词： Vitis vinifera Viral Disease Small rna Deep Sequencing RT-PCR

超保守rna uc.102-uc.106及其宿主基因OLA1在不同组织中的差异表达

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中国病理生理杂志 2024年第8期40卷 1361-1368页

作者：王鑫张毅许晗魏子辰庞磊赵明超郁多男扬州大学医学院/江苏省非编码rna基础与临床转化重点实验室江苏扬州225009 扬州大学附属医院消化内科江苏扬州225003

目的:本研究旨在探究超保守rna uc.102-uc.106基因簇及其宿主基因Obg样ATP酶1(OLA1)在C57BL/6J小鼠不同组织器官中的表达差异。方法:选取5只8~10周龄的健康雄性C57BL/6J小鼠,在正常生理条件下采集不同组织器官(包括肝脏、睾丸、骨髓、... 详细信息

目的:本研究旨在探究超保守rna uc.102-uc.106基因簇及其宿主基因Obg样ATP酶1(OLA1)在C57BL/6J小鼠不同组织器官中的表达差异。方法:选取5只8~10周龄的健康雄性C57BL/6J小鼠,在正常生理条件下采集不同组织器官(包括肝脏、睾丸、骨髓、大脑、肾脏、血液、肺、结肠、胸腺、脾脏、胃、心脏、淋巴结和膀胱)。同时使用磁珠分选技术提取骨髓血细胞,包括B细胞、巨噬细胞、有核红细胞和成熟红细胞。通过RT-qPCR技术,以GAPDH作为内参照,检测uc.102-uc.106和OLA1 mrna的表达量。结果:OLA1 mrna在C57BL/6J小鼠大脑、淋巴结、睾丸和胸腺中呈高水平表达,在肝脏、脾脏、肺、结肠和外周血中呈低水平表达(Prna表达基本相反,但在睾丸组织中两者均呈高水平表达(P<0.05)。在血细胞中,OLA1和uc.102-uc.106在B细胞中的表达水平最高,在成熟红细胞中的表达水平最低(P<0.05)。结论:OLA1基因和uc.102-uc.106基因簇在C57BL/6J小鼠的不同组织器官及血细胞中均有表达且存在差异。值得注意的是,OLA1基因和uc.102-uc.106基因簇在小鼠睾丸中均呈高水平表达,表明OLA1基因和uc.102-uc.106基因簇可能与雄性小鼠的生殖功能密切相关。

关键词：超保守rna uc.102-uc.106基因簇 OLA1基因 C57BL/6J小鼠