Histone mRNA Regulation in Development

发育中的组蛋白 mRNA 调控

基本信息

批准号：
8536306
负责人：
Robert J Duronio
金额：
$ 57.89万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-05-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8536306
关键词：
Address Anabolism Animals Architecture Area Biochemical Biochemical Genetics Biological Models Cell Culture System Cell Cycle Cell Cycle Regulation Cells Cellular biology Chromatin Modeling Chromatin Structure Chromosomes Complex Cultured Cells DNA DNA biosynthesis Defect Development Drosophila genus Elements Gene Expression Genes Genetic Genetic Transcription Genome Goals Histones Human In Vitro Mammalian Cell Mammals Messenger RNA Metabolism Methods Modeling Molecular Mutation Nuclear Organism Pattern Poly A Polyadenylation Pre-mRNA Polyadenylation Factor Process Production Proteins RNA Processing RNA biosynthesis Reaction Recruitment Activity Regulation Reporter Genes Role S Phase Specific qualifier value System Tail Testing Time Translating U7 Small Nuclear Ribonucleoprotein Variant developmental genetics endonuclease fly genome wide association study in vivo light microscopy mRNA Cleavage and Polyadenylation Factors mRNA Precursor novel particle polyadenylated messenger RNA

项目摘要

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.

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尾巴尾部的真核生物mRNA，而是在保守的茎上。与组蛋白变体的对比mRNA，例如H3.3和H2.V由聚腺苷酸化的mRNA编码。所有五种组蛋白蛋白的基因都聚集在后生基因组中，组蛋白基因表达所需的因子位于组蛋白基因附近。我们将确定使用果蝇作为模型系统，尤其是组蛋白基因座体在组蛋白mRNA代谢中的作用，确定体内复制依赖性组蛋白mRNA的坐标要求。我们将使用生化和遗传学方法来确定1。HLB组件中的结构要求闪存和NPAT有效地产生正确处理正确的组蛋白mRNA所需将确定CPSF100，并在体外和体内阐明Symplekin在组蛋白前MRNA加工中的作用。