Maki Yoshihama

RPG: the Ribosomal Protein Gene database

RPG (http://ribosome.miyazaki-med.ac.jp/) is a new database that provides detailed information about ribosomal protein (RP) genes. It contains data from humans and other organisms, including Drosophila melanogaster, Caenorhabditis elegans, Saccharo myces cerevisiae, Methanococcus jannaschii and Escherichia coli. Users can search the database by gene name and organism. Each record includes sequences (genomic, cDNA and amino acid sequences), intron/exon structures, genomic locations and information about orthologs. In addition, users can view and compare the gene structures of the above organisms and make multiple amino acid sequence alignments. RPG also provides information on small nucleolar RNAs (snoRNAs) that are encoded in the introns of RP genes.

Characteristics and clustering of human ribosomal protein genes

BackgroundThe ribosome is a central player in the translation system, which in mammals consists of four RNA species and 79 ribosomal proteins (RPs). The control mechanisms of gene expression and the functions of RPs are believed to be identical. Most RP genes have common promoters and were therefore assumed to have a unified gene expression control mechanism.ResultsWe systematically analyzed the homogeneity and heterogeneity of RP genes on the basis of their expression profiles, promoter structures, encoded amino acid compositions, and codon compositions. The results revealed that (1) most RP genes are coordinately expressed at the mRNA level, with higher signals in the spleen, lymph node dissection (LND), and fetal brain. However, 17 genes, including the P protein genes (RPLP0, RPLP1, RPLP2), are expressed in a tissue-specific manner. (2) Most promoters have GC boxes and possible binding sites for nuclear respiratory factor 2, Yin and Yang 1, and/or activator protein 1. However, they do not have canonical TATA boxes. (3) Analysis of the amino acid composition of the encoded proteins indicated a high lysine and arginine content. (4) The major RP genes exhibit a characteristic synonymous codon composition with high rates of G or C in the third-codon position and a high content of AAG, CAG, ATC, GAG, CAC, and CTG.ConclusionEleven of the RP genes are still identified as being unique and did not exhibit at least some of the above characteristics, indicating that they may have unknown functions not present in other RP genes. Furthermore, we found sequences conserved between human and mouse genes around the transcription start sites and in the intronic regions. This study suggests certain overall trends and characteristic features of human RP genes.

Analysis of ribosomal protein gene structures: implications for intron evolution.

Many spliceosomal introns exist in the eukaryotic nuclear genome. Despite much research, the evolution of spliceosomal introns remains poorly understood. In this paper, we tried to gain insights into intron evolution from a novel perspective by comparing the gene structures of cytoplasmic ribosomal proteins (CRPs) and mitochondrial ribosomal proteins (MRPs), which are held to be of archaeal and bacterial origin, respectively. We analyzed 25 homologous pairs of CRP and MRP genes that together had a total of 527 intron positions. We found that all 12 of the intron positions shared by CRP and MRP genes resulted from parallel intron gains and none could be considered to be “conserved,” i.e., descendants of the same ancestor. This was supported further by the high frequency of proto-splice sites at these shared positions; proto-splice sites are proposed to be sites for intron insertion. Although we could not definitively disprove that spliceosomal introns were already present in the last universal common ancestor, our results lend more support to the idea that introns were gained late. At least, our results show that MRP genes were intronless at the time of endosymbiosis. The parallel intron gains between CRP and MRP genes accounted for 2.3% of total intron positions, which should provide a reliable estimate for future inferences of intron evolution.

Phase distribution of spliceosomal introns: implications for intron origin

BackgroundThe origin of spliceosomal introns is the central subject of the introns-early versus introns-late debate. The distribution of intron phases is non-uniform, with an excess of phase-0 introns. Introns-early explains this by speculating that a fraction of present-day introns were present between minigenes in the progenote and therefore must lie in phase-0. In contrast, introns-late predicts that the nonuniformity of intron phase distribution reflects the nonrandomness of intron insertions.ResultsIn this paper, we tested the two theories using analyses of intron phase distribution. We inferred the evolution of intron phase distribution from a dataset of 684 gene orthologs from seven eukaryotes using a maximum likelihood method. We also tested whether the observed intron phase distributions from 10 eukaryotes can be explained by intron insertions on a genome-wide scale. In contrast to the prediction of introns-early, the inferred evolution of intron phase distribution showed that the proportion of phase-0 introns increased over evolution. Consistent with introns-late, the observed intron phase distributions matched those predicted by an intron insertion model quite well.ConclusionOur results strongly support the introns-late hypothesis of the origin of spliceosomal introns.

RNAcentral: a comprehensive database of non-coding RNA sequences

Abstract RNAcentral is a database of non-coding RNA (ncRNA) sequences that aggregates data from specialised ncRNA resources and provides a single entry point for accessing ncRNA sequences of all ncRNA types from all organisms. Since its launch in 2014, RNAcentral has integrated twelve new resources, taking the total number of collaborating database to 22, and began importing new types of data, such as modified nucleotides from MODOMICS and PDB. We created new species-specific identifiers that refer to unique RNA sequences within a context of single species. The website has been subject to continuous improvements focusing on text and sequence similarity searches as well as genome browsing functionality. All RNAcentral data is provided for free and is available for browsing, bulk downloads, and programmatic access at http://rnacentral.org/.RNAcentral is a database of non-coding RNA (ncRNA) sequences that aggregates data from specialised ncRNA resources and provides a single entry point for accessing ncRNA sequences of all ncRNA types from all organisms. Since its launch in 2014, RNAcentral has integrated twelve new resources, taking the total number of collaborating database to 22, and began importing new types of data, such as modified nucleotides from MODOMICS and PDB. We created new species-specific identifiers that refer to unique RNA sequences within a context of single species. The website has been subject to continuous improvements focusing on text and sequence similarity searches as well as genome browsing functionality. All RNAcentral data is provided for free and is available for browsing, bulk downloads, and programmatic access at http://rnacentral.org/.

snOPY: a small nucleolar RNA orthological gene database

BackgroundSmall nucleolar RNAs (snoRNAs) are a class of non-coding RNAs that guide the modification of specific nucleotides in ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). Although most non-coding RNAs undergo post-transcriptional modifications prior to maturation, the functional significance of these modifications remains unknown. Here, we introduce the snoRNA orthological gene database (snOPY) as a tool for studying RNA modifications.FindingssnOPY provides comprehensive information about snoRNAs, snoRNA gene loci, and target RNAs. It also contains data for orthologues from various species, which enables users to analyze the evolution of snoRNA genes. In total, 13,770 snoRNA genes, 10,345 snoRNA gene loci, and 133 target RNAs have been registered. Users can search and access the data efficiently using a simple web interface with a series of internal links. snOPY is freely available on the web at http://snoopy.med.miyazaki-u.ac.jp.ConclusionssnOPY is the database that provides information about the small nucleolar RNAs and their orthologues. It will help users to study RNA modifications and snoRNA gene evolution.

The human ribosomal protein L6 gene in a critical region for Noonan syndrome

AbstractWe 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 5′ 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.

Intron dynamics in ribosomal protein genes.

The role of spliceosomal introns in eukaryotic genomes remains obscure. A large scale analysis of intron presence/absence patterns in many gene families and species is a necessary step to clarify the role of these introns. In this analysis, we used a maximum likelihood method to reconstruct the evolution of 2,961 introns in a dataset of 76 ribosomal protein genes from 22 eukaryotes and validated the results by a maximum parsimony method. Our results show that the trends of intron gain and loss differed across species in a given kingdom but appeared to be consistent within subphyla. Most subphyla in the dataset diverged around 1 billion years ago, when the “Big Bang” radiation occurred. We speculate that spliceosomal introns may play a role in the explosion of many eukaryotes at the Big Bang radiation.

Correction: New Maximum Likelihood Estimators for Eukaryotic Intron Evolution

Correction: Structure Modeling of All Identified G Protein–Coupled Receptors in the Human Genome Yang Zhang, Mark E. DeVries, Jeffrey Skolnick DOI: 10.1371/journal.pcbi.0020013 In PLoS Computational Biology, volume 2, issue 2: The URL provided for the GPCR model database in the published article is no longer active. The database is now located at http://cssb.biology.gatech.edu/skolnick/files/gpcr/gpcr.html.