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Analysis of highly organized functions of the ribosome

核糖体高度组织功能的分析

基本信息

批准号：
14035103
负责人：
KENMOCHI Naoya
金额：
$ 39.87万
依托单位：
University of Miyazaki (2004-2006)宮崎医科大学 (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2006
项目状态：
已结题

项目摘要

The ribosome is an essential and complex macromolecule responsible for protein synthesis in all organisms. In this study, we have carried out a systematic analysis of ribosomal protein (RP) genes and small nucleolar RNA (snoRNA) genes, and developed animal models to investigate the relationship between the ribosomal abnormalities and human diseases.1. We have constructed an RP gene database (RPG, http://ribosome.med.miyazaki-u.ac.jp). RPG is highly accessed (>2,000 hits everyday) and has become a standard database for RP gene analysis.2. We also constructed a snoRNA Orthological database (snoOPY, http://snoopy.med.miyazaki-u.ac.jp/), which provides a powerful tool for studying the ribosomal RNA modifications.3. We have determined the promoter structures and expression profiles of RP genes in humans and mouse, which allowed us to identify the transcription factors involved in co-regulated RP gene expression, for a better understanding of the molecular mechanism of ribosome synthesis.4. We have developed zebrafish models with defects in RP genes by inhibiting the mRNA translation using morpholino antisense oligos. The snoRNA expression was also inhibited in the same way. Analyses of these embryos suggested that there is a novel ribosome-dependent regulatory mechanism of gene expression, which should be the key to understanding the 'ribosomapathy'.

核糖体是所有生物体中负责蛋白质合成的重要且复杂的大分子。本研究对核糖体蛋白（RP）基因和核仁小RNA（snoRNA）基因进行了系统分析，并建立了核糖体异常与人类疾病关系的动物模型.我们构建了RP基因数据库（RPG，http://ribosome.med.miyazaki-u.ac.jp）。RPG的访问量很高（每天超过2，000次点击），已成为RP基因分析的标准数据库。我们还构建了一个snoRNA Orthological数据库（snoOPY，http：//snopy.med.miyazaki-u.ac.jp/），为研究核糖体RNA修饰提供了有力的工具.我们确定了人和小鼠RP基因的启动子结构和表达谱，这使我们能够确定参与共调控RP基因表达的转录因子，为更好地理解核糖体合成的分子机制奠定基础.我们已经开发了斑马鱼模型与缺陷RP基因通过抑制mRNA翻译使用吗啉代反义寡核苷酸。snoRNA的表达也以同样的方式被抑制。对这些胚胎的分析表明，存在一种新的依赖于核糖体的基因表达调控机制，这应该是理解“核糖体病”的关键。