Abstract

INTRODUCTION

The most wellknown function of small nucleolar ribonucleoprotein particles (designated snoRNPs in Eukaryotes and sRNPs in Archaea) is to catalyze the 2′-O-ribose methylation (C/D snoRNPs) and pseudouridinylation (H/ACA snoRNPs) of ribosomal RNAs. The RNA components of snoRNP complexes are responsible for sequence specificity to the RNA target and possess no inherent catalytic or modification activity. Direct base pairing between the snoRNA and the target RNA provides site specificity for the catalytic protein subunits associated with the guide snoRNA, resulting in post-transcriptional modification of the target RNA.

Ribosomal RNAs are not the only target for snoRNP-directed nucleoside modification; for example, in Archaea, some C/D sRNPs (as snoRNA homologs are known in these organisms) direct post-transcriptional 2′-O-methylation of tRNA (Clouet d'Orval et al. 2001; Tang et al. 2005). In addition to their most well-known roles in 2′-O-methylation and psuedouridylation of ribosomal RNAs, some snoRNPs perform essential roles in pre-rRNA cleavages, and others function as rRNA chaperones during the assembly of the ribosome (Sáez-Vasquez et al. 2004). snoRNAs have also been shown to be associated with Prader-Willi syndrome, and other snoRNAs have putative binding sites flanking alternative splice junctions (Cavaillé et al. 2000; Skryabin et al. 2007; Bazeley et al. 2008; Ding et al. 2008).

snoRNAs fall into two major families based on their function and secondary structure: C/D and H/ACA. The primary function of the H/ACA snoRNP complex is to convert specific uridine ribonucleotides in the target RNA to pseudouridines. The H/ACA small nucleolar motif is composed of two conserved sequence elements: the Hinge box (H) between the two RNA hairpins, and an ACA sequence at the 3′ end of the RNA (Balakin et al. 1996). C/D snoRNAs act as guide RNAs for site-specific 2′-O-methylation. The C/D box motif in eukaryotic and archaeal sRNPs is characterized by two terminal conserved sequences, box C (AUGAUGA) and box D (CUGA), and two similar internal C′/D′ motifs.

The proteins in the snoRNP complex are remarkably diverse but share some common features. These proteins can be divided into four subtypes: archaeal H/ACA sRNA proteins (L7Ae, CBF5, NOP10, and GAR1), eukaryotic H/ACA snoRNA (Gar1p, Cbf5p, Nhp2p, and Nop10p), archaeal C/D sRNA (L7Ae, Nop56/58, fibrillarin), and eukaryotic C/D snoRNA (Snu13p, Nop56p, Nop58p, and fibrillarin). This diversity underscores the need for a snoRNP database that includes both the RNA and protein sequences.

Several snoRNA databases exist (Samarsky and Fournier 1999; Brown et al. 2003; Xie et al. 2007). All of these are focused on specific types of snoRNAs or snoRNAs from specific sources, and do not include snoRNA-associated proteins. The snoRNP database is the most comprehensive assembly of experimentally confirmed and computationally predicted snoRNAs and their proteins. The database, with its search engine, collection of ~9000 snoRNA sequences, and nearly 600 snoRNP protein sequences, serves the snoRNP community and can be found at http://evolveathome.com/snoRNA/snoRNA.php.

DATABASE OVERVIEW

The identification of noncoding (e.g., microRNA, RNase P RNA, 6S RNA, and snoRNA) RNAs in genomic and metagenomic sequences has proven to be a difficult computational task. Numerous algorithms have been created to identify putative noncoding RNAs, including snoRNAs. The snoRNA community has benefited from the creation of several important algorithms capable of identifying putative snoRNAs, such as snoTARGET, snoReport, Snoscan, snoGPS, and snoSeeker (Lowe and Eddy 1999; McCutcheon and Eddy 2003; Accardo et al. 2004; Hüttenhofer et al. 2004; Ghazal et al. 2005; Schattner et al. 2005; Yang et al. 2006; Bazeley et al. 2008; Hertel et al. 2008). This rapid expansion of robust bioinformatics tools has resulted in the identification of a large number of putative snoRNAs embedded in chromosomal, contig, and metagenomic sequences. However, because many of the predicted snoRNAs are embedded, but not annotated, in large sequences and are not available individually, it is difficult for researchers to access individual snoRNA sequences. Furthermore, none of the current snoRNA databases contain the proteins associated with snoRNP complexes. To address the lack of a central specialized repository, facilitate rapid searches of snoRNA/protein sequences, and support novel snoRNA-related algorithms in the future, the snoRNP database was created.

ACKNOWLEDGMENT

Footnotes

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