生物信息学进展教学jw生物信息学进展.pptxVIP

生物信息学进展教学jw生物信息学进展第1页/共45页 生物信息学进展MicroRNA Systems Biology第2页/共45页 IntroductionCentral dogma of molecular biologyChallenged by tiny fragments of noncoding RNAmiRNA, ~22 nucleotides, negatively regulate protein-coding genes, central posttranscriptional regulators of gene expressionVia imperfect base pairing to the 3’UTR of target mRNAs: repression of protein production or mRNA degradation第3页/共45页 IntroductionHave been found in diverse plants, animals, some viruses and even algae (藻类) speciesAll multicellular eukaryotes, and perhaps some unicellular eukaryotes, utilize these RNAs to regulate gene expression第4页/共45页 IntroductionSome researchers claimed that more than 1,000 miRNAs in human genome (Bentwich et al. 2005)718 miRNAs in human (2009-03)940 miRNAs in human (2010-04)1048 miRNAs in human (2011-04)1921 miRNAs in human (2012-03)2042 miRNAs in human (2013-03)第5页/共45页 IntroductionExperimental analysis: 100 to 200 target mRNAs are repressed and destabilized by a single miRNA (Krutzfeldt et al. 2005; Lim et al. 2005; Yu et al. 2007a)Estimated: more than one third of human genes are potentially regulated by miRNAs第6页/共45页 IntroductionThe following discoveries offer new insight into another layer of gene regulation；Animals that fail to produce certain mature miRNAs are unable to survive or reproduce；A single miRNA can be sufficient to cause cancer in mice (Costinean et al. 2006).第7页/共45页 内容microRNA的生物合成microRNA的生物功能microRNA与人类疾病※microRNA调控细胞网络microRNA对信号网络调控microRNA对基因调控网络调控microRNA对代谢网络调控microRNA对蛋白质互作网络调控microRNA调控网络的motif分析第8页/共45页 First discovered in C. elegansby Victor AmbrosTermed ‘miRNAs’19932001200220032004Uniformannotation systemRegistry database (miRBase)Individual miRNAexpression in variousspecies and tissuesFirst reportmiRNA expressionin cancersFirst application of array technologymacro-arrayRT PCRmicrobeadmicroarray2005Global picturein human cancers2007474 humanmiRNAsFebruary 1Other types ofnoncoding RNAIntegrationmiRNA with TFAt least800 miRNAs225 humanmi