Analysis of highly organized functions of the ribosome

核糖体是所有生物体中负责蛋白质合成的重要而复杂的大分子。在这项研究中，我们对核糖体蛋白(RP)基因和小核仁RNA(SnoRNA)基因进行了系统的分析，并建立了动物模型来研究核糖体异常与人类疾病的关系。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2,000次点击)，并已成为RP基因分析的标准数据库。我们还构建了snoRNA Orthology数据库(Snoopy，http://snoopy.med.miyazaki-u.ac.jp/)，)，为研究核糖体RNA的修饰提供了有力的工具。我们已经确定了RP基因在人和小鼠体内的启动子结构和表达谱，这使得我们能够确定参与共同调控RP基因表达的转录因子，从而更好地理解核糖体合成的分子机制。我们利用吗啡反义寡核苷酸抑制rp基因的翻译，建立了具有rp基因缺陷的斑马鱼模型。SnoRNA的表达也以同样的方式受到抑制。对这些胚胎的分析表明，存在一种新的核糖体依赖的基因表达调控机制，这应该是理解核糖病的关键。

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'.