Histone mRNA Regulation in Development

描述（由申请人提供）：动物复制依赖性组蛋白mRNA是唯一缺乏polyA尾末端而不是保守茎环的真核mRNA。相反，组蛋白变体的mRNA，例如H3.3和H2.v，由多腺苷酸化的mRNA编码。所有五种组蛋白的基因都聚集在后生动物基因组中，组蛋白基因表达所需的因子位于组蛋白基因附近。我们将确定的复制依赖性组蛋白mRNA的协调表达在体内使用果蝇作为模型系统的要求，特别是组蛋白基因座体在组蛋白mRNA代谢中的作用。我们将使用生物化学和遗传学方法来确定1。HLB组分FLASH和NPAT中的结构要求是有效生产适当加工的组蛋白mRNA所需的，2.在组蛋白基因座中的序列，其指定在组蛋白基因座处形成HLB，和3.组蛋白裂解因子的组成，其中包含多聚腺苷酸化因子Symplekin，CPSF 73和CPSF 100，将被确定和Symplekin在组蛋白前mRNA的加工中的作用，在体外和体内阐明。

DESCRIPTION (provided by applicant): Animal replication-dependent histone mRNAs are the only eukaryotic mRNAs that lack a polyA tail ending instead in a conserved stemloop. In contrast mRNAs for histone variants, e.g. H3.3 and H2.v, are encoded by polyadenylated mRNAs. The genes for all five histone proteins are clustered in metazoan genomes, and factors required for histone gene expression are localized near the histone genes. We will determine the requirements for the coordinate expression of the replication-dependent histone mRNAs in vivo using Drosophila as a model system, and in particular the role of the Histone Locus Body in histone mRNA metabolism. We will use both biochemical and genetic approaches to determine 1. The structural requirements in the HLB components FLASH and NPAT required for efficient production of properly processed histone mRNA, 2. The sequences in the histone gene locus that specifies the formation of the HLB at the histone locus and 3. The composition of the histone cleavage factor, which contains polyadenylation factors Symplekin, CPSF73 and CPSF100, will be determined and the role of Symplekin in histone pre-mRNA processing in vitro and in vivo elucidated.