The ribosome, as a catalyst for protein synthesis, is universal and essential for all organisms. Here we describe the structure of the genes encoding human ribosomal proteins (RPs) and compare this class of genes among several eukaryotes. Using genomic and full-length cDNA sequences, we characterized 73 RP genes and found that (1) transcription starts at a C residue within a characteristic oligopyrimidine tract; (2) the promoter region is GC rich, but often has a TATA box or similar sequence element; (3) the genes are small (4.4 kb), but have as many as 5.6 exons on average; (4) the initiator ATG is in the first or second exon and is within ± 5 bp of the first intron boundaries in about half of cases; and (5) 5Ј-and 3Ј-UTRs are significantly smaller (42 bp and 56 bp, respectively) than the genome average. Comparison of RP genes from humans, Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae revealed the coding sequences to be highly conserved (63% homology on average), although gene size and the number of exons vary. The positions of the introns are also conserved among these species as follows: 44% of human introns are present at the same position in either D. melanogaster or C. elegans, suggesting RP genes are highly suitable for studying the evolution of introns.[The sequence data described in this paper have been submitted to the DDBJ/EMBL/GenBank databases under accession nos. AB055762-AB055780, AB056456, AB061820-AB061859, AB062066-AB062071, and AB070559.]The ribosome is the cellular organelle responsible for protein synthesis in all cells. Recent analyses of the ribosome's structure using X-ray crystallography have enhanced our understanding of the structural basis of ribosome function (Ban et al. 2000;Schluenzen et al. 2000;Wimberly et al. 2000;Yusupov et al. 2001). In contrast, comparatively little is known about ribosome biogenesis, especially in higher eukaryotes. In mammalian cells, the biogenesis of cytoplasmic ribosomes requires assembly of 4 RNA molecules and 79 different proteins (Wool 1979). With the exception of two proteins, all of these components are present as single copies within the ribosome. Typically, mammalian cells contain ∼4 ‫ן‬ 10 6 cytoplasmic ribosomes, which account for 80% of all cellular RNA and 5%-10% of cellular proteins.Investigation of the mechanism that controls the coordinated expression of these components is a challenge. Three different RNA polymerases are involved in production of these RNAs and proteins, RNA polymerase I (POL I) is involved in production of the 28S, 18S, and 5.8S rRNAs, POL II in production of ribosomal proteins (RPs), and POL III in production of the 5S rRNA. The amino acid sequences of all rat and human RPs have been deduced (Wool et al. 1996), and the nucleotide sequences of thousands of eukaryotic rRNAs are now known (The Ribosome Database Project; Maidak et al. 2001). On the other hand, only a handful of mammalian RP genes have been studied in terms of their genomic structure. Unlike rRNAs, which are encoded by several ...

Ribosome is responsible for protein synthesis in all organisms and ribosomal proteins (RPs) play important roles in the formation of a functional ribosome. L11 was recently shown to regulate p53 activity through a direct binding with MDM2 and abrogating the MDM2-induced p53 degradation in response to ribosomal stress. However, the studies were performed in cell lines and the significance of this tumor suppressor function of L11 has yet to be explored in animal models. To investigate the effects of the deletion of L11 and its physiological relevance to p53 activity, we knocked down the rpl11 gene in zebrafish and analyzed the p53 response. Contrary to the cell line-based results, our data indicate that an L11 deficiency in a model organism activates the p53 pathway. The L11-deficient embryos (morphants) displayed developmental abnormalities primarily in the brain, leading to embryonic lethality within 6–7 days post fertilization. Extensive apoptosis was observed in the head region of the morphants, thus correlating the morphological defects with apparent cell death. A decrease in total abundance of genes involved in neural patterning of the brain was observed in the morphants, suggesting a reduction in neural progenitor cells. Upregulation of the genes involved in the p53 pathway were observed in the morphants. Simultaneous knockdown of the p53 gene rescued the developmental defects and apoptosis in the morphants. These results suggest that ribosomal dysfunction due to the loss of L11 activates a p53-dependent checkpoint response to prevent improper embryonic development.

Ribosomes are responsible for protein synthesis in all cells. Ribosomal protein S19 (RPS19) is one of the 79 ribosomal proteins (RPs) in vertebrates. Heterozygous mutations in RPS19 have been identified in 25% of patients with Diamond-Blackfan anemia (DBA), but the relationship between RPS19 mutations and the pure red-cell aplasia of DBA is unclear. In this study, we developed an RPS19-deficient zebrafish by knocking down rps19 using a Morpholino antisense oligo. The RPS19-deficient animals showed a dramatic decrease in blood cells as well as deformities in the head and tail regions at early developmental stages. These phenotypes were rescued by injection of zebrafish rps19 mRNA, but not by injection of rps19 mRNAs with mutations that have been identified in DBA patients. Our results indicate that rps19 is essential for hematopoietic differentiation during early embryogenesis. The effects were specific to rps19, but knocking down the genes for three other RPs, rpl35, rpl35a and rplp2, produced similar phenotypes, suggesting that these genes might have a common function in zebrafish erythropoiesis. The RPS19-deficient zebrafish will provide a valuable tool for investigating the molecular mechanisms of DBA development in humans.

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We have determined the genomic structure of the human ribosomal protein L6 gene (RPL6) and assigned it to the interval containing the Noonan syndrome locus. RPL6 spans 4415 bp and consists of seven exons and six introns. The first exon is only 19 bp in length, containing a 5Ј non-coding region and a polypyrimidine tract. The second exon starts with the initiator ATG. Although the overall structure of the protein is highly conserved among mammalian species, there is significant variation in the N-terminal portion. We have refined the position of RPL6, using two different radiation hybrid panels. RPL6 was mapped to chromosome 12q24.1 between the markers D12S84 and D12S861, which is in the critical region for Noonan syndrome.

A plexiform variant of leiomyoma of the esophagus in a 51-year-old woman is reported. The patient was diagnosed with a tumor of the esophagus in an X-ray mass survey of the upper gastrointestinal tract. She was referred to the Ryukyu University Hospital for further examination. She appeared healthy with no complaints. Upper gastrointestinal series revealed an oval, well-defined filling defect in the lower esophagus just above the esophagogastric junction. Endoscopy revealed an undulating bulge covered with normal esophageal mucosa. Endoscopic ultrasonography showed a sharply demarcated hypoechoic mural tumor with internal linear pattern, with no evidence of penetration into the surrounding tissue. These findings were evaluated as consistent with a leiomyoma. Removing the tumor by enucleation was easily accomplished. Unexpectedly, on gross inspection, the tumor was a plexiform type, mimicking a plexiform neurofibroma. Light and electron microscopic examination and immunohistochemistry of the tumor tissue confirmed leiomyoma. Since the enucleation of the tumor, the patient has been free of recurrence and symptoms for 1.5 years at the time of this report.

Initial palliation with bPAB enables AoV diameter growth in some patients, improving the likelihood of conventional total repair adaptation rate, particularly for CoA or IAA type A.