snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs

The snoRNA-LBME-db is a dedicated database containing human C/D box and H/ACA box small nucleolar RNAs (snoRNAs), and small Cajal body-specific RNAs (scaRNAs). C/D box and H/ACA box snoRNAs are part of ribonucleoparticles that guide 2′-O-ribose methylation and pseudouridilation, respectively, of selected residues of 28S, 18S or 5.8S rRNAs or of the spliceosomal U6 RNA. Similarly, scaRNAs guide modifications of the spliceosomal RNAs transcribed by RNA polymerase II (U1, U2, U4, U5 and U12) and are often composed of both C/D box and H/ACA box domains. However, some snoRNAs do not function as modification guide RNAs, but rather as RNA chaperones during the maturation of pre-rRNA. The database was built by a compilation of the literature, and comprises human sno/scaRNAs that were experimentally verified, as well as the human orthologs of snoRNAs that were cloned in other vertebrate species, and some snoRNAs that are predicted by bioinformatics search in loci submitted to genomic imprinting, but have not all been experimentally verified. For each entry, the database identifies the modified nucleotide(s) in the target RNA(s), indicates the corresponding predicted base pairing, gives a few pertinent references and provides a link to the position of the sno/scaRNA on the UCSC Genome Browser. The ‘Find guide RNA’ function allows one to find the sno/scaRNAs predicted to guide the modification of a particular nucleotide in the rRNA and spliceosomal RNA sequences. The ‘Browse’ function allows one to download the sequences of selected sno/scaRNAs in the FASTA format. The database is available online at . It can also be accessed from the human UCSC Genome Browser via the sno/miRNA track

Autism genetic database (AGD): a comprehensive database including autism susceptibility gene-CNVs integrated with known noncoding RNAs and fragile sites

<p>Abstract</p> <p>Background</p> <p>Autism is a highly heritable complex neurodevelopmental disorder, therefore identifying its genetic basis has been challenging. To date, numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism, but most discoveries either fail to be replicated or account for a small effect. Thus, in most cases the underlying causative genetic mechanisms are not fully understood. In the present work, the Autism Genetic Database (AGD) was developed as a literature-driven, web-based, and easy to access database designed with the aim of creating a comprehensive repository for all the currently reported genes and genomic copy number variations (CNVs) associated with autism in order to further facilitate the assessment of these autism susceptibility genetic factors.</p> <p>Description</p> <p>AGD is a relational database that organizes data resulting from exhaustive literature searches for reported susceptibility genes and CNVs associated with autism. Furthermore, genomic information about human fragile sites and noncoding RNAs was also downloaded and parsed from miRBase, snoRNA-LBME-db, piRNABank, and the MIT/ICBP siRNA database. A web client genome browser enables viewing of the features while a web client query tool provides access to more specific information for the features. When applicable, links to external databases including GenBank, PubMed, miRBase, snoRNA-LBME-db, piRNABank, and the MIT siRNA database are provided.</p> <p>Conclusion</p> <p>AGD comprises a comprehensive list of susceptibility genes and copy number variations reported to-date in association with autism, as well as all known human noncoding RNA genes and fragile sites. Such a unique and inclusive autism genetic database will facilitate the evaluation of autism susceptibility factors in relation to known human noncoding RNAs and fragile sites, impacting on human diseases. As a result, this new autism database offers a valuable tool for the research community to evaluate genetic findings for this complex multifactorial disorder in an integrated format. AGD provides a genome browser and a web based query client for conveniently selecting features of interest. Access to AGD is freely available at <url>http://wren.bcf.ku.edu/</url>.</p

Autism genetic database (AGD): a comprehensive database including autism susceptibility gene-CNVs integrated with known noncoding RNAs and fragile sites

Background: Autism is a highly heritable complex neurodevelopmental disorder, therefore identifying its genetic basis has been challenging. To date, numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism, but most discoveries either fail to be replicated or account for a small effect. Thus, in most cases the underlying causative genetic mechanisms are not fully understood. In the present work, the Autism Genetic Database (AGD) was developed as a literature-driven, web-based, and easy to access database designed with the aim of creating a comprehensive repository for all the currently reported genes and genomic copy number variations (CNVs) associated with autism in order to further facilitate the assessment of these autism susceptibility genetic factors. Description: AGD is a relational database that organizes data resulting from exhaustive literature searches for reported susceptibility genes and CNVs associated with autism. Furthermore, genomic information about human fragile sites and noncoding RNAs was also downloaded and parsed from miRBase, snoRNA-LBME-db, piRNABank, and the MIT/ICBP siRNA database. A web client genome browser enables viewing of the features while a web client query tool provides access to more specific information for the features. When applicable, links to external databases including GenBank, PubMed, miRBase, snoRNA-LBME-db, piRNABank, and the MIT siRNA database are provided. Conclusion: AGD comprises a comprehensive list of susceptibility genes and copy number variations reported to-date in association with autism, as well as all known human noncoding RNA genes and fragile sites. Such a unique and inclusive autism genetic database will facilitate the evaluation of autism susceptibility factors in relation to known human noncoding RNAs and fragile sites, impacting on human diseases. As a result, this new autism database offers a valuable tool for the research community to evaluate genetic findings for this complex multifactorial disorder in an integrated format. AGD provides a genome browser and a web based query client for conveniently selecting features of interest. Access to AGD is freely available at http://wren.bcf.ku.edu/ webcite

Structural and Functional Characterization of Ribosomal Protein Gene Introns in Sponges

Ribosomal protein genes (RPGs) are a powerful tool for studying intron evolution. They exist in all three domains of life and are much conserved. Accumulating genomic data suggest that RPG introns in many organisms abound with non-protein-coding-RNAs (ncRNAs). These ancient ncRNAs are small nucleolar RNAs (snoRNAs) essential for ribosome assembly. They are also mobile genetic elements and therefore probably important in diversification and enrichment of transcriptomes through various mechanisms such as intron/exon gain/loss. snoRNAs in basal metazoans are poorly characterized. We examined 449 RPG introns, in total, from four demosponges: Amphimedon queenslandica, Suberites domuncula, Suberites ficus and Suberites pagurorum and showed that RPG introns from A. queenslandica share position conservancy and some structural similarity with “higher” metazoans. Moreover, our study indicates that mobile element insertions play an important role in the evolution of their size. In four sponges 51 snoRNAs were identified. The analysis showed discrepancies between the snoRNA pools of orthologous RPG introns between S. domuncula and A. queenslandica. Furthermore, these two sponges show as much conservancy of RPG intron positions between each other as between themselves and human. Sponges from the Suberites genus show consistency in RPG intron position conservation. However, significant differences in some of the orthologous RPG introns of closely related sponges were observed. This indicates that RPG introns are dynamic even on these shorter evolutionary time scales

Structural Characterization of FAU Gene/Protein from Marine Sponge Suberites domuncula

Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV) ubiquitously expressed (FAU) gene is down-regulated in human prostate, breast and ovarian cancers. Moreover, its dysregulation is associated with poor prognosis in breast cancer. Sponges (Porifera) are animals without tissues which branched off first from the common ancestor of all metazoans. A large majority of genes implicated in human cancers have their homologues in the sponge genome. Our study suggests that FAU gene from the sponge Suberites domuncula reflects characteristics of the FAU gene from the metazoan ancestor, which have changed only slightly during the course of animal evolution. We found pro-apoptotic activity of sponge FAU protein. The same as its human homologue, sponge FAU increases apoptosis in human HEK293T cells. This indicates that the biological functions of FAU, usually associated with “higher” metazoans, particularly in cancer etiology, possess a biochemical background established early in metazoan evolution. The ancestor of all animals possibly possessed FAU protein with the structure and function similar to evolutionarily more recent versions of the protein, even before the appearance of true tissues and the origin of tumors and metastasis. It provides an opportunity to use pre-bilaterian animals as a simpler model for studying complex interactions in human cancerogenesis

Mining small RNA sequencing data: a new approach to identify small nucleolar RNAs in Arabidopsis

Small nucleolar RNAs (snoRNAs) are noncoding RNAs that direct 2′-O-methylation or pseudouridylation on ribosomal RNAs or spliceosomal small nuclear RNAs. These modifications are needed to modulate the activity of ribosomes and spliceosomes. A comprehensive repertoire of snoRNAs is needed to expand the knowledge of these modifications. The sequences corresponding to snoRNAs in 18–26-nt small RNA sequencing data have been rarely explored and remain as a hidden treasure for snoRNA annotation. Here, we showed the enrichment of small RNAs at Arabidopsis snoRNA termini and developed a computational approach to identify snoRNAs on the basis of this characteristic. The approach successfully uncovered the full-length sequences of 144 known Arabidopsis snoRNA genes, including some snoRNAs with improved 5′- or 3′-end annotation. In addition, we identified 27 and 17 candidates for novel box C/D and box H/ACA snoRNAs, respectively. Northern blot analysis and sequencing data from parallel analysis of RNA ends confirmed the expression and the termini of the newly predicted snoRNAs. Our study especially expanded on the current knowledge of box H/ACA snoRNAs and snoRNA species targeting snRNAs. In this study, we demonstrated that the use of small RNA sequencing data can increase the complexity and the accuracy of snoRNA annotation

Critical association of ncRNA with introns

It has been widely acknowledged that non-coding RNAs are master-regulators of genomic functions. However, the significance of the presence of ncRNA within introns has not received proper attention. ncRNA within introns are commonly produced through the post-splicing process and are specific signals of gene transcription events, impacting many other genes and modulating their expression. This study, along with the following discussion, details the association of thousands of ncRNAs—snoRNA, miRNA, siRNA, piRNA and long ncRNA—within human introns. We propose that such an association between human introns and ncRNAs has a pronounced synergistic effect with important implications for fine-tuning gene expression patterns across the entire genome

Expanding the SnoRNA Interaction Network: Conservation of Guiding Function in Vertebrates

Small nucleolar RNAs (snoRNAs) are one of the most abundant and evolutionary ancient group of small non-coding RNAs. Their main function is to target chemical modifications of ribosomal RNAs (rRNAs) and small nuclear (snRNAs). They fall into two classes, box C/D snoRNAs and box H/ACA snoRNAs, which are clearly distinguished by conserved sequence motifs and the type of modification that they govern. The box H/ACA snoRNAs are responsible for targeting pseudouridylation sites and the box C/D snoRNAs for directing 2’-O-methylation of ribonucleotides. A subclass that localize to the Cajal bodies, termed scaRNAs, are responsible for methylation and pseudouridylation of snRNAs. In addition an amazing diversity of non-canonical functions of individual snoRNAs arose. The modification patterns in rRNAs and snRNAs are retained during evolution making it even possible to project them from yeast onto human. The stringent conservation of modification sites and the slow evolution of rRNAs and snRNAs contradicts the rapid evolution of snoRNA sequences. Recent studies that incorporate high-throughput sequencing experiments still identify undetected snoRNAs even in well studied organisms as human. The snoRNAbase, which has been the standard database for human snoRNAs has not been updated ince 2006 and misses these new data. Along with the lack of a centralized data collection across species, which incorporates also snoRNA class specific characteristics the need to integrate distributed data from literature and databases into a comprehensive snoRNA set arose. Although several snoRNA studies included pro forma target predictions in individual species and more and more studies focus on non-canonical functions of subclasses a systematic survey on the guiding function and especially functional homologies of snoRNAs was not available. To establish a sound set of snoRNAs a computational snoRNA annotation pipeline, named snoStrip that identifies homologous snoRNAs in related species was employed. For large scale investigation of the snoRNA function, state-of-the-art target pedictions were performed with our software RNAsnoop and PLEXY. Further, a new measure the Interaction Conservation Index (ICI) was developed to evaluate the conservation of snoRNA function. The snoStrip pipeline was applied to vertebrate species, where the genome sequence has been available. In addition, it was used in several ncRNA annotation studies (48 avian, spotted gar) of newly assembled genomes to contribute the snoRNA genes. Detailed target analysis of the new vertebrate snoRNA set revealed that in general functions of homologous snoRNAs are evolutionarily stable, thus, members of the same snoRNA family guide equivalent modifications. The conservation of snoRNA sequences is high at target binding regions while the remaining sequence varies significantly. In addition to elucidating principles of correlated evolution it was possible, with the help of the ICI measure, to assign functions to previously orphan snoRNAs and to associate snoRNAs as partners to known but so far unexplained chemical modifications. As further pattern redundant guiding became apparent. For many modification sites more than one snoRNA encodes the appropriate antisense element (ASE), which could ensure constant modification through snoRNAs that have different expression patterns. Furthermore, predictions of snoRNA functions in conjunction with sequence conservation could identify distant homologies. Due to the high overall entropy of snoRNA sequences, such relationships are hard to detect by means of sequence homology search methods alone. The snoRNA interaction network was further expanded through novel snoRNAs that were detected in data from high-throughput experiments in human and mouse. Through subsequent target analysis the new snoRNAs could immediately explain known modifications that had no appropriate snoRNA guide assigned before. In a further study a full catalog of expressed snoRNAs in human was provided. Beside canonical snoRNAs also recent findings like AluACAs, sno-lncRNAs and extraordinary short SNORD-like transcripts were taken into account. Again the target analysis workflow identified undetected connections between snoRNA guides and modifications. Especially some species/clade specific interactions of SNORD-like genes emerged that seem to act as bona fide snoRNA guides for rRNA and snRNA modifications. For all high confident new snoRNA genes identified during this work official gene names were requested from the HUGO Gene Nomenclature Committee (HGNC) avoiding further naming confusion