Control of Histone mRNA Levels

组蛋白 mRNA 水平的控制

• 批准号: 7986704
• 负责人: WILLIAM F. MARZLUFF
• 金额: $ 10.11万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-17 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7986704
• 关键词: Anabolism; Binding; Binding Proteins; Cell Cycle; Cell Nucleus; Cells; Chromatin; Chromosomes; Cleaved cell; Complex; Coupled; Cytoplasm; DNA; DNA biosynthesis; Elements; Equilibrium; Genes; Genetic Translation; Grant; Histones; In Vitro; Introns; Mammalian Cell; Mediating; Messenger RNA; Metabolism; Modification; Pathway interactions; Phase; Phosphotransferases; Play; Poly A; Process; Protein Biosynthesis; Proteins; Reaction; Recruitment Activity; Regulation; Role; Signal Pathway; Signal Transduction Pathway; Staging; Structure; System; Tail; Translations; U7 Small Nuclear Ribonucleoprotein; cell growth; chemotherapy; chromosome replication; in vivo; mRNA Precursor; mRNA Transcript Degradation; novel; protein complex

DESCRIPTION (provided by applicant): As mammalian cells go through the cell cycle they replicate their chromosomes during S-phase. Successful replication requires not only replication of DNA but also the synthesis of large amounts of histone proteins to package the newly replicated DNA into chromatin. The histone mRNAs are a unique class of mRNAs and are the only mRNAs that lack a polyA tail. They end instead in a conserved stemloop which is the major cis- element responsible for coordinate regulation of histone mRNAs are the posttranscriptional level. Biosynthesis of histone mRNAs requires a single processing reaction, cleavage of the pre-mRNA to form the mature mRNA. This reaction is regulated during the cell cycle, as is the stability of histone mRNA. We propose to identify the factor(s) directly involved in cleavage of histone pre-mRNA, by purifying the processing complex and to also identify which of these factors that are involved in regulating this process. Histone mRNAs are rapidly degraded when DNA replication is inhibited. We will determine the pathway of histone mRNA degradation and the factors involved in initiating and regulating the degradation of histone mRNAs. Finally we will elucidate the signal transduction pathways that transmit the information that DNA replication has ceased in the nucleus to degradation of the histone mRNA in the cytoplasm. Laymans description: Histone proteins are the proteins complexed with DNA in the chromosomes. Proper chromosome replication requires synthesis of both DNA and histones, and these two processes are tightly coupled. We will determine the factors critical for both histone mRNA synthesis and degradation, and novel factors provide potential new chemotherapy targets, as well as helping us to understand the control of cell growth.

描述（由申请人提供）：随着哺乳动物细胞经过细胞周期，它们在S期间复制其染色体。成功的复制不仅需要复制DNA，而且还需要大量组蛋白蛋白的合成，以将新复制的DNA包装成染色质。组蛋白mRNA是独特的mRNA类，是唯一缺乏polya尾巴的mRNA。相反，它们以保守的STEMLOOP结束，这是负责组蛋白mRNA的坐标调节的主要元素是转录后水平。组蛋白mRNA的生物合成需要单个加工反应，即裂解前mRNA以形成成熟的mRNA。该反应在细胞周期中受到调节，组蛋白mRNA的稳定性也是如此。我们建议通过纯化加工复合物并确定与调节此过程有关的这些因素中的哪些因素，以确定直接参与组蛋白前MRNA裂解的因子。当DNA复制被抑制时，组蛋白mRNA会迅速降解。我们将确定组蛋白mRNA降解的途径以及启动和调节组蛋白mRNA降解的因素。最后，我们将阐明信号转导途径传播DNA复制已在细胞核中停止的信息，从而降解了细胞质中组蛋白mRNA的降解。外行描述：组蛋白是与染色体中DNA复合的蛋白质。正确的染色体复制需要同时合成DNA和组蛋白，并且这两个过程紧密耦合。我们将确定对组蛋白mRNA合成和降解至关重要的因素，新的因素提供了潜在的新化疗靶标，并帮助我们了解细胞生长的控制。