Analysis of highly organized functions of the ribosome

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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'.