- Data Note
- Open Access
snOPY: a small nucleolar RNA orthological gene database
© Yoshihama et al.; licensee BioMed Central Ltd. 2013
- Received: 26 August 2013
- Accepted: 21 October 2013
- Published: 23 October 2013
Small 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.
snOPY 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.
snOPY 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.
- RNA modification
Large-scale sequencing and transcriptome analyses have revealed that most of the genome is transcribed and that there are a large number of non-protein-coding transcripts present in the cell . Functional non-coding RNAs (ncRNAs) include micro RNAs (miRNAs), short interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs), which play important roles in biological processes such as gene expression, gene silencing, and RNA processing . In addition, there are many classical essential ncRNAs, including ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs), and tRNAs. Some of these RNAs are known to undergo post-transcriptional modifications [3–5]. Experimental results have shown that deficiencies in RNA-modifying enzymes lead to embryonic death in mice, and the loss of rRNA modification leads to developmental defects in zebrafish, which signifies the importance of RNA modifications for the proper functioning of ncRNAs [6, 7]. Although many modification sites have been identified , the functions of these modifications remain unknown.
Small nucleolar RNAs (snoRNAs) play key roles in the RNA modification process. These RNAs function as guide RNAs for the site-specific modification of target RNAs such as rRNAs and snRNAs . Over the last decade, a large number of snoRNAs have been identified experimentally or computationally in various species [10, 11]. These RNAs are encoded by three types of genomic loci, i.e., intronic gene loci, polycistronic gene loci (clusters), and monocistronic gene loci (independent) . The snoRNA genes of different loci must be expressed in different ways but in a coordinated manner. For example, for the maturation of human 28S rRNA, 98 distinct snoRNA genes need to be expressed simultaneously from 65 independent loci. It is still unclear how the expression of these snoRNAs is regulated in a synchronized manner.
We have constructed the snoRNA orthological gene database (snOPY) as a tool for studying RNA modifications and snoRNA gene evolution. This database provides comprehensive information about snoRNAs, snoRNA gene loci, and target RNAs. In addition, it includes manually curated orthologous gene data for each gene. This unique database enables users to analyze not only snoRNAs but also their targets and gene organization in various species.
Ribosomal RNA (rRNA)
Small nuclear RNA (snRNA)
There are three types of snoRNA gene loci: intronic, polycistronic, and monocistronic [9, 14]. In intronic loci, the snoRNA gene is located within the intron of protein-coding or non-protein-coding genes (host gene) and transcribed simultaneously with its host gene under the control of the host gene promoter. The maturation of snoRNA transcripts is achieved via the splicing and subsequent processing of the host gene. In the animal kingdom, most snoRNA genes are expressed from introns . The polycistronic loci contain multiple snoRNA genes that are organized into a cluster and transcribed from a single promoter, whereas the monocistronic loci contain a single snoRNA gene that is expressed from its own promoter. In plants and yeast, most of the snoRNA genes exhibit either polycistronic or monocistronic expression [15, 16].
rRNAs and snRNAs are the major targets of snoRNAs. In general, the number of modified nucleotides depends on the length of the target RNA. For example, human 28S rRNA and U2 snRNA contain 119 and 13 modification sites, respectively. However, there are many orphan snoRNAs whose targets remain to be determined.
snOPY also contains information about snoRNA orthologues. The identification of the orthologues using common homology search techniques such as BLAST is difficult because the sequence conservation between snoRNAs from different species is very low (Figure 2). Although there are some short conserved motifs, BLAST often fails to identify the correct counterparts. Therefore, we focused on the sequence conservation between the target RNAs such as rRNAs rather than the snoRNA sequences themselves to identify the orthologues. We performed sequence alignment of the target RNAs from different species using ClustalW , then mapped the modification sites on that alignment. If the modified nucleotide is aligned at the same position, we assumed the snoRNA that guides this modification as an orthologue.
Utility and discussion
Each snoRNA entry page provides basic information about the locus, including the snoRNA gene sequence, type of box motif, and genomic position (Figure 3D). Information relating to the gene locus and target RNA is also provided, and these items are linked to more detailed descriptions (Figure 3E). Users can retrieve orthologues and perform multiple sequence alignments via this page (Figure 3F). The locus entry pages show schematics of the locus structure and sequence, as well as other information about the locus (Figure 3G). The target RNA entry pages show complete RNA sequences and modification sites (Figure 3H). When available, the snoRNAs involved in these modifications are also shown, with links to the individual snoRNA entry page. Users can access a list of all target RNAs via the “Target RNA” link at the top of each page (Figure 3A).
The orthologues table page shows the orthologous relationships between snoRNA genes from various species (Figure 3I). The default setting includes four selected species, Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, and Saccharomyces cerevisiae, which are well studied and widely referenced species. Users can select any species for comparison and readily access the reference data from the default setting.
At present, there exist several other databases for snoRNAs, including snoRNA-LBME-db , Yeast snoRNA Database , Plant snoRNA Database , and the sno/scaRNAbase . These databases provide very useful information about the snoRNAs from particular organisms. However, users are unable to compare the snoRNAs from various species. On the other hand, snOPY provides data from a wide variety of species, which enables users to perform comparative analysis very efficiently.
snOPY is freely available on the web at http://snoopy.med.miyazaki-u.ac.jp.
We thank Dr. Jun-ichi Iwakiri and Dr. Sayomi Higa (University of the Ryukyus) for help and advice with the database development and Ms. Mariko Nagatomo and Ms. Shiori Yasukawa for their help in collecting the data. This work was supported by JSPS KAKENHI Grant Numbers 22370065, 238043, 248045, and 24659476.
- The ENCODE Project Consortium: An integrated encyclopedia of DNA elements in the human genome. Nature. 2012, 489: 57-74. 10.1038/nature11247.PubMed CentralView ArticleGoogle Scholar
- Amaral PP, Dinger ME, Mercer TR, Mattick JS: The eukaryotic genome as an RNA machine. Science. 2008, 319: 1787-1789. 10.1126/science.1155472.PubMedView ArticleGoogle Scholar
- Decatur WA, Fournier MJ: rRNA modifications and ribosome function. Trends Biochem Sci. 2002, 27: 344-351. 10.1016/S0968-0004(02)02109-6.PubMedView ArticleGoogle Scholar
- Darzacq X, Jady BE, Verheggen C, Kiss AM, Bertrand E, Kiss T: Cajal body-specific small nuclear RNAs: A novel class of 2′-O-methylation and pseudouridylation guide RNAs. EMBO J. 2002, 21: 2746-2756. 10.1093/emboj/21.11.2746.PubMedPubMed CentralView ArticleGoogle Scholar
- Johansson M, Byström A: Transfer RNA modifications and modifying enzymes in Saccharomyces cerevisiae. Fine-Tuning of RNA Functions by Modification and Editing, Topics in Current Genetics. Volume 12. Edited by: Grosjean H. 2005, Springer: Heidelberg/Berlin, 87-120.Google Scholar
- Newton K, Petfalski E, Tollervey D, Caceres JF: Fibrillarin is essential for early development and required for accumulation of an intron-encoded small nucleolar RNA in the mouse. Mol Cell Biol. 2003, 23: 8519-8527. 10.1128/MCB.23.23.8519-8527.2003.PubMedPubMed CentralView ArticleGoogle Scholar
- Higa-Nakamine S, Suzuki T, Uechi T, Chakraborty A, Nakajima Y, Nakamura M, Hirano N, Suzuki T, Kenmochi N: Loss of ribosomal RNA modification causes developmental defects in zebrafish. Nucleic Acids Res. 2012, 40: 391-398. 10.1093/nar/gkr700.PubMedPubMed CentralView ArticleGoogle Scholar
- Machnicka MA, Milanowska K, Osman Oglou O, Purta E, Kurkowska M, Olchowik A, Januszewski W, Kalinowski S, Dunin-Horkawicz S, Rother KM, Helm M, Bujnicki JM, Grosjean H: MODOMICS: a database of RNA modification pathways—2013 update. Nucleic Acids Res. 2013, 41 (Database issue): D262-D267.PubMedPubMed CentralView ArticleGoogle Scholar
- Matera AG, Terns RM, Terns MP: Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol. 2007, 8: 209-220. 10.1038/nrm2124.PubMedView ArticleGoogle Scholar
- Castle JC, Armour CD, Löwer M, Haynor D, Biery M, Bouzek H, Chen R, Jackson S, Johnson JM, Rohl CA, Raymond CK: Digital genome-wide ncRNA expression, including snoRNAs, across 11 human tissues using polyA-neutral amplification. PLoS One. 2010, 5: e11779-10.1371/journal.pone.0011779.PubMedPubMed CentralView ArticleGoogle Scholar
- Morita K, Saito Y, Sato K, Oka K, Hotta K, Sakakibara Y: Genome-wide searching with base-pairing kernel functions for noncoding RNAs: computational and expression analysis of snoRNA families in Caenorhabditis elegans. Nucleic Acids Res. 2009, 37: 999-1009. 10.1093/nar/gkn1054.PubMedPubMed CentralView ArticleGoogle Scholar
- Kiss-Laszlo Z, Henry Y, Bachellerie JP, Caizergues-Ferrer M, Kiss T: Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell. 1996, 85: 1077-1088. 10.1016/S0092-8674(00)81308-2.PubMedView ArticleGoogle Scholar
- Ni J, Tien AL, Fournier MJ: Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA. Cell. 1997, 89: 565-573. 10.1016/S0092-8674(00)80238-X.PubMedView ArticleGoogle Scholar
- Tycowski KT, Kolev NG, Conrad NK, Fok V, Steitz JA: The ever-growing world of small nuclear ribonucleoproteins. The RNA world. Edited by: Gesteland RF, Cech TR, Atkins JF. 2006, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 327-368.Google Scholar
- Brown JW, Clark GP, Leader DJ, Simpson CG, Lowe T: Multiple snoRNA gene clusters from Arabidopsis. RNA. 2001, 7: 1817-1832.PubMedPubMed CentralGoogle Scholar
- Piekna-Przybylska D, Decatur WA, Fournier MJ: New bioinformatic tools for analysis of nucleotide modifications in eukaryotic rRNA. RNA. 2007, 13: 305-312. 10.1261/rna.373107.PubMedPubMed CentralView ArticleGoogle Scholar
- Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG: Clustal W and clustal X version 2.0. Bioinformatics. 2007, 23: 2947-2948. 10.1093/bioinformatics/btm404.PubMedView ArticleGoogle Scholar
- Lestrade L, Weber MJ: snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs. Nucleic Acids Res. 2006, 34: D158-D162. 10.1093/nar/gkj002.PubMedPubMed CentralView ArticleGoogle Scholar
- Brown JW, Echeverria M, Qu LH, Lowe TM, Bachellerie JP, Hüttenhofer A, Kastenmayer JP, Green PJ, Shaw P, Marshall DF: Plant snoRNA database. Nucleic Acids Res. 2003, 31: 432-435. 10.1093/nar/gkg009.PubMedPubMed CentralView ArticleGoogle Scholar
- Xie J, Zhang M, Zhou T, Hua X, Tang L, Wu W: Sno/scaRNAbase: a curated database for small nucleolar RNAs and cajal body-specific RNAs. Nucleic Acids Res. 2007, 35: D183-D187. 10.1093/nar/gkl873.PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.