The outbreak of COVID-19 caused by SARS-CoV-2 is spreading worldwide,with the pathogenesis mostly unclear.Both virus and host-derived microRNA(miRNA)play essential roles in the pathology of virus infection.This study ...The outbreak of COVID-19 caused by SARS-CoV-2 is spreading worldwide,with the pathogenesis mostly unclear.Both virus and host-derived microRNA(miRNA)play essential roles in the pathology of virus infection.This study aims to uncover the mechanism for SARS-CoV-2 pathogenicity from the perspective of miRNA.We scanned the SARS-CoV-2 genome for putative miRNA genes and miRNA targets and conducted in vivo experiments to validate the virus-encoded miRNAs and their regulatory role on the putative targets.One of such virus-encoded miRNAs,MR147-3p,was overexpressed that resulted in significantly decreased transcript levels of all of the predicted targets in human,i.e.,EXOC7,RAD9A,and TFE3 in the virus-infected cells.The analysis showed that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs.Additionally,the genomic mutation of SARS-CoV-2 contributed to the changed miRNA repository and targets,suggesting a possible role of miRNAs in the attenuated phenotype of SARS-CoV-2 during its evolution.This study provided a comprehensive view of the miRNA-involved regulatory system during SARS-CoV-2 infection,indicating possible antiviral therapeutics against SARS-CoV-2 through intervening miRNA regulation.展开更多
MicroRNAs （miRNAs） are endogenous 22-nt RNAs, which play important regulatory roles by post-transcriptional gene silencing. A computational strategy has been developed for the identification of conserved miRNAs base...MicroRNAs （miRNAs） are endogenous 22-nt RNAs, which play important regulatory roles by post-transcriptional gene silencing. A computational strategy has been developed for the identification of conserved miRNAs based on features of known metazoan miRNAs in red flour beetle （Tribolium castaneum）, which is regarded as one of the major laboratory models of arthropods. Among 118 putative miRNAs, 47% and 53% of the predicted miRNAs from the red flour beetle are harbored by known protein-coding genes （intronic） and genes located outside （intergenic miRNA）, respectively. There are 31 intronic miRNAs in the same transcriptional orientation as the host genes, which may share RNA polymerase II and spliceosomal machinery with their host genes for their biogenesis. A hypothetical feed-back model has been proposed based on the analysis of the relationship between intronic miRNAs and their host genes in the development of red flour beetle.展开更多
流行性感冒(简称“流感”)是由流感病毒引起的急性呼吸道传染疾病,据世界卫生组织统计,流感每年可导致300万~500万严重病例,其中29万~65万病例死亡,给社会带来沉重的经济负担,是一个世界性的公共卫生难题。研究发现宿主细胞中存在多条...流行性感冒(简称“流感”)是由流感病毒引起的急性呼吸道传染疾病,据世界卫生组织统计,流感每年可导致300万~500万严重病例,其中29万~65万病例死亡,给社会带来沉重的经济负担,是一个世界性的公共卫生难题。研究发现宿主细胞中存在多条信号通路参与对流感病毒感染的应答,越来越多的研究表明宿主miRNAs通过直接或间接的方式,在流感病毒感染、复制的不同阶段发挥着重要调控作用。本文综合分析了目前关于宿主细胞miRNA对流感病毒复制调控的研究进展,对不同的miRNA具体的调控机制进行系统地归类总结后发现:甲型流感病毒(Influenza A virus,IAV)的PB1、PB2、NA、NP、M1基因是宿主miRNA直接抑制病毒复制的主要靶基因,而在间接调控过程中宿主miRNA主要作用在RIG-I样受体信号通路,Jak-STAT信号通路和Toll样受体信号通路三条流感病毒应答信号途径中,以上发现将更有助于全面理解宿主miRNA对于流感病毒调控网络和宿主细胞与流感病毒的互作机制。展开更多
基金This work was supported by National Natural Science Foundation of China(NSFC)grant No.81671983 and 81871628 to X.L.,NSFC grant No.81703306China Postdoctoral Science Foundation(2017M611867)+1 种基金Postdoctoral Science Foundation of Jiangsu Province(1701119C)to Z.L.,NSFC grant No.81902027Natural Science Foundation of Jiangsu Province to J.W.(BK20171045).
文摘The outbreak of COVID-19 caused by SARS-CoV-2 is spreading worldwide,with the pathogenesis mostly unclear.Both virus and host-derived microRNA(miRNA)play essential roles in the pathology of virus infection.This study aims to uncover the mechanism for SARS-CoV-2 pathogenicity from the perspective of miRNA.We scanned the SARS-CoV-2 genome for putative miRNA genes and miRNA targets and conducted in vivo experiments to validate the virus-encoded miRNAs and their regulatory role on the putative targets.One of such virus-encoded miRNAs,MR147-3p,was overexpressed that resulted in significantly decreased transcript levels of all of the predicted targets in human,i.e.,EXOC7,RAD9A,and TFE3 in the virus-infected cells.The analysis showed that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs.Additionally,the genomic mutation of SARS-CoV-2 contributed to the changed miRNA repository and targets,suggesting a possible role of miRNAs in the attenuated phenotype of SARS-CoV-2 during its evolution.This study provided a comprehensive view of the miRNA-involved regulatory system during SARS-CoV-2 infection,indicating possible antiviral therapeutics against SARS-CoV-2 through intervening miRNA regulation.
文摘MicroRNAs （miRNAs） are endogenous 22-nt RNAs, which play important regulatory roles by post-transcriptional gene silencing. A computational strategy has been developed for the identification of conserved miRNAs based on features of known metazoan miRNAs in red flour beetle （Tribolium castaneum）, which is regarded as one of the major laboratory models of arthropods. Among 118 putative miRNAs, 47% and 53% of the predicted miRNAs from the red flour beetle are harbored by known protein-coding genes （intronic） and genes located outside （intergenic miRNA）, respectively. There are 31 intronic miRNAs in the same transcriptional orientation as the host genes, which may share RNA polymerase II and spliceosomal machinery with their host genes for their biogenesis. A hypothetical feed-back model has been proposed based on the analysis of the relationship between intronic miRNAs and their host genes in the development of red flour beetle.
文摘流行性感冒(简称“流感”)是由流感病毒引起的急性呼吸道传染疾病,据世界卫生组织统计,流感每年可导致300万~500万严重病例,其中29万~65万病例死亡,给社会带来沉重的经济负担,是一个世界性的公共卫生难题。研究发现宿主细胞中存在多条信号通路参与对流感病毒感染的应答,越来越多的研究表明宿主miRNAs通过直接或间接的方式,在流感病毒感染、复制的不同阶段发挥着重要调控作用。本文综合分析了目前关于宿主细胞miRNA对流感病毒复制调控的研究进展,对不同的miRNA具体的调控机制进行系统地归类总结后发现:甲型流感病毒(Influenza A virus,IAV)的PB1、PB2、NA、NP、M1基因是宿主miRNA直接抑制病毒复制的主要靶基因,而在间接调控过程中宿主miRNA主要作用在RIG-I样受体信号通路,Jak-STAT信号通路和Toll样受体信号通路三条流感病毒应答信号途径中,以上发现将更有助于全面理解宿主miRNA对于流感病毒调控网络和宿主细胞与流感病毒的互作机制。
