人类细小病毒B19基因组中央polyA位点选择性使用的分子调控机制

项目名称： 人类细小病毒B19基因组中央polyA位点选择性使用的分子调控机制

项目编号： No.31270208

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 关武祥

作者单位： 中国科学院武汉病毒研究所

项目金额： 80万元

中文摘要： 细小病毒嗜红细胞属B19病毒通过呼吸道、血液和母婴传播等方式感染人导致多种疾病如感染性红斑（五号病）、急慢性关节炎和再生障碍性贫血等。B19病毒基因组含有两个polyA信号，直接调控病毒蛋白mRNA的表达水平。位于基因组中央的polyA信号（pA）p抑制病毒全长pre-mRNA的转录、第二个内含子剪切和结构蛋白mRNA的产生，（pA）p的使用成为病毒转录和转录后调控的关键环节，相关研究十分有限。本项目拟通过病毒感染系统研究病毒进入敏感细胞后的染色质状态及其修饰对polyA信号（pA）p使用的影响；构建（pA）p位点polyA信号报告质粒及突变体转染Cos7细胞研究DNA复制对内含子剪切以及（pA）p使用的影响；鉴定与病毒内含子增强子结合的蛋白及其影响（pA）p使用的机制。全面探讨polyA信号（pA）p的使用机制不仅阐明病毒转录和转录后调控的分子生物学机理，而且为病毒的防治提供新的思路。

中文关键词： 细小病毒B19；类染色质结构；DAC；复制；RNA剪切

英文摘要： Human parvovirus B19, a member of human erythrovirus genus, causes a number of human diseases, such as erythema infectiosum, acute and chrnoic arthropathy, aplastic crysis. B19 virus is spread primarily by infected respiratory droplets, blood borne transmission and vertical transmission from pregnant mother to baby. The viral genome contains two polyadenylation sites which control the abundance of different viral mRNAs. Its proximal polyadenylation signal (pA)p, which is in the middle of virus genome, not only blocks the transcription of its full length pre-mRNA, but also competes with the second intron splicing which is a necessary step to produce structure protein mRNA. Therefore, regulation of polyadenylation at (pA)p plays an important role both transcriptionally and posttranscriptionallly in the virus life cycle.However, the mechnism of polyadenylation at (pA)p is largely unknown. Based on our published work, we sought to study polyadenylation regulation at (pA)p by different factors such as viral DNA chromatin state, DNA replication of the viral genome and proteins that bind to intron splicing enhancer. The regulation of polyadenylation at (pA)p will be elucidated by the chromatin state and modification after virus entry into permissive cells. Whether DNA replication of viral genome affects polyadenylation

英文关键词： B19V；Chromatin-like structure；DAC；Replication；RNA splicing