6. MRC Human Immunology Unit,MRC Weatherall Institute of Molecular Medicine,Radcliffe Department of Medicine,University of Oxford,Oxford OX3 7FZ,UK;Chinese Academy of Medical Sciences(CAMS),CAMS Oxford Institute(COI),Nuffield Department of Medicine,University of Oxford,Oxford OX3 7FZ,UK
8. Chinese Academy of Medical Sciences(CAMS),CAMS Oxford Institute(COI),Nuffield Department of Medicine,University of Oxford,Oxford OX3 7FZ,UK;Target Discovery Institute,Centre for Medicines Discovery,Nuffield Department of Medicine,University of Oxford,Oxford OX3 7FZ,UK
9. Department of Electrical Engineering and Computer Science,and Christopher S.Bond Life Sciences Center,University of Missouri,Columbia MO 65211,USA
折叠
摘要
2012年首次报道了稻米来源的miRNA的跨界调控.通过改良的草药提取方法和高通量测序技术,本研究从245种中药(traditional Chinese medicine,TCM)中获得了73677287条小核酸(small RNA,sRNA)序列,其中包含20758257条去冗余后的独特序列.本研究构建了本草小核酸数据库(Bencao(herbal)small RNA Atlas)(http://bencao.bmicc.cn),同时基于序列分析,进行sRNAs注释并建立了本草小核酸命名系统.经计算分析,本草小核酸数据库中的21757条miRNAs与收录于miRBase数据库中的植物miRNAs的特征图谱高度一致.多种软件计算分析结果表明,人类所有编码基因都有可能受来自本草小核酸数据库中的sRNAs的调控,本研究通过实验验证了其中一部分的预测计算结果.这些结果显示,本草来源的sRNAs可能是中草药的新的重要药效活性成分.本研究提出了基于本草小核酸数据库的寡核苷酸药物的研发路径和中药处方的优化策略路线图.此外,中药汤剂体(decocto-some)是中药水煎液中的脂质纳米颗粒,其质量约占中药水煎液的0.5％～2.5％,却展示出显著的药效.本研究提出了新的可用于定量衡量草药药效标准的本草指数,包括小分子化合物(small-molecule compounds,SM)、蛋白多肽(protein peptides,P)、核酸(nucleic acid,N)、非核酸非蛋白大分子化合物(large-molecule compounds,LM)和门捷列夫周期表中的相关元素(E).本研究构建的本草小核酸数据库,可用于寡核苷酸药物的开发和植物药的优化,并为易(壹)医学理论提供了科学依据.
Abstract
Cross-kingdom herbal miRNA was first reported in 2012.Using a modified herbal extraction protocol,we obtained 73677287 sequences by RNA-seq from 245 traditional Chinese Medicine(TCM),of which 20758257 were unique sequences.We constructed a Bencao(herbal)small RNA(sRNA)Atlas(http://bencao.bmicc.cn),annotated the sequences by sequence-based clustering,and created a nomenclature system for Bencao sRNAs.The profiles of 21,757 miRNAs in the Atlas were highly consistent with those of plant miRNAs in miRBase.Using software tools,our results demonstrated that all human genes might be regulated by sRNAs from the Bencao sRNA Atlas,part of the predicted human target genes were experimentally validated,suggesting that Bencao sRNAs might be one of the main bioactive components of herbal medicines.We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions.Moreover,the decoctosome,a lipo-nano particle consisting of 0.5％-2.5％of the decoction,demonstrated potent medical effects.We propose a Bencao(herbal)Index,including small-molecule compounds(SM),protein peptides(P),nucleic acid(N),non-nucleic and non-proteinogenic large-molecule compounds(LM)and elements from Mendeleev's periodic table(E),to quantitatively measure the medical effects of botanic medicine.The Bencao sRNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine,and may provide potential remedies for the theory and practice of one medicine.
关键词
小核酸/中药水煎液/跨界调控/中药/寡核苷酸药物/核酸治疗/本草小核酸数据库
Key words
small RNA/herbal decoction/cross-kingdom regulation/traditional Chinese medicine/RNA oligonucleotide drug/RNA therapeutics/Bencao small RNA Atlas
万方数据