Background: Small nucleolar RNAs (snoRNAs) are one of the most ancient families amongst non-protein-coding RNAs. They are ubiquitous in Archaea and Eukarya but absent in bacteria. Their main function is to target chemical modifications of ribosomal RNAs. 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 chemical modification that they govern. Similarly to microRNAs, snoRNAs appear in distinct families of homologs that affect homologous targets. In animals, snoRNAs and their evolution have been studied in much detail. In plants, however, their evolution has attracted comparably little attention. Results: In order to chart the phylogenetic distribution of individual snoRNA families in plants, we applied a sophisticated approach for identifying homologs of known plant snoRNAs across the plant kingdom. In response to the relatively fast evolution of snoRNAs, information on conserved sequence boxes, target sequences, and secondary structure is combined to identify additional snoRNAs. We identified 296 families of snoRNAs in 24 species and traced their evolution throughout the plant kingdom. Many of the plant snoRNA families comprise paralogs. We also found that targets are well-conserved for most snoRNA families. Conclusions: The sequence conservation of snoRNAs is sufficient to establish homologies between phyla. The degree of this conservation tapers off, however, between land plants and algae. Plant snoRNAs are frequently organized in highly conserved spatial clusters. As a resource for further investigations we provide carefully curated and annotated alignments for each snoRNA family under investigation.

Background: Small nucleolar RNAs (snoRNAs) are one of the most ancient families amongst non-protein-coding RNAs. They are ubiquitous in Archaea and Eukarya but absent in bacteria. Their main function is to target chemical modifications of ribosomal RNAs. 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 chemical modification that they govern. Similarly to microRNAs, snoRNAs appear in distinct families of homologs that affect homologous targets. In animals, snoRNAs and their evolution have been studied in much detail. In plants, however, their evolution has attracted comparably little attention. Results: In order to chart the phylogenetic distribution of individual snoRNA families in plants, we applied a sophisticated approach for identifying homologs of known plant snoRNAs across the plant kingdom. In response to the relatively fast evolution of snoRNAs, information on conserved sequence boxes, target sequences, and secondary structure is combined to identify additional snoRNAs. We identified 296 families of snoRNAs in 24 species and traced their evolution throughout the plant kingdom. Many of the plant snoRNA families comprise paralogs. We also found that targets are well-conserved for most snoRNA families. Conclusions: The sequence conservation of snoRNAs is sufficient to establish homologies between phyla. The degree of this conservation tapers off, however, between land plants and algae. Plant snoRNAs are frequently organized in highly conserved spatial clusters. As a resource for further investigations we provide carefully curated and annotated alignments for each snoRNA family under investigation.

Circular RNAs (circRNAs) sind eine große Klasse endogener RNAs, die in Organismen vorkommen, die RNA-Transkripte durch Spleißen prozessieren. Sie sind Produkte des „backsplicing“ – einer Art des alternativen Spleißens, bei der das 3‘-Ende eines Exons mit einer vorgelagerten 5‘-„splice site“ verbunden wird. Trotz ihrer Abundanz und spezifischen Expressionsmustern sind in vivo-Funktionen von circRNAs größtenteils unbekannt. Wir haben den existierenden Kenntnisstand systematisiert und diesen in Form von circBase frei zugänglich gemacht. circBase ist eine Online-Datenbank, in der circRNA-Datensätze abgerufen und im genomischen Kontext durchsucht und visualisiert werden können. Für die Arbeit mit Hochdurchsatz-circRNA-Daten haben wir des Weiteren die Software ciRcus entwickelt. Um mehr bezüglich circRNA-Expression und möglicher Funktionen zu lernen, haben wir die Expressionsmuster im Säugetiergehirn umfassend erforscht. Mithilfe von eigenen und öffentlich zugänglichen RNA-Sequenzierungsdaten haben wir Tausende von neuralen circRNAs in Mensch und Maus entdeckt. circRNAs waren während der neuronalen Differenzierung und Reifung insgesamt hochreguliert, stark angereichert in Synapsen, und oft differentiell exprimiert im Vergleich zu ihren mRNA-Isoformen. Außerdem haben wir gezeigt, dass viele circRNAs zwischen Mensch und Maus konserviert sind. Schließlich haben wir in vivo-Funktionen von Cdr1as erforscht - einer konservierten und im Gehirn hoch exprimierten circRNA, die stark von microRNA (miRNA)-Effektor-Komplexen gebunden ist und zahlreiche miR-7-Bindestellen sowie eine Bindestelle für miR-671 aufweist. „Knockout“-Tiere, bei denen der Cdr1as-Lokus deletiert wurde, zeigten ein gestörtes sensomotorisches „gating“ und dysfunktionale synaptische Übertragung. Die Expression von miR-7 und miR-671 war in verschiedenen Hirnregionen der Tiere dereguliert. Die Expression von „immediate early“-Genen, von denen einige miR-7-Zielgene sind, war erhöht. / circular RNAs (circRNAs) are a large class of endogenous RNAs present in organisms that process RNA transcripts by splicing. They are products of backsplicing - alternative splicing reactions where the 3’ end of an exon is spliced to an upstream 5’ splice site. Despite their abundance and tissue- and developmental-stage-specific expression patterns, their in vivo functions are largely unknown. We systematized the existing knowledge on circRNAs and made it freely available by developing circBase - an online database where circRNA datasets can be accessed, downloaded and browsed within the genomic context. Another technical challenge was addressed by developing ciRcus - a software package for working with high-throughput circRNA data, which allowed us to routinely handle, explore, annotate, quantify and integrate circRNA data with the external sources of biological data. To learn more about circRNA expression and potential functions, we have explored the expression patterns of circRNAs in the mammalian brain. Using own and public RNA-seq data, we discovered thousands of neural circRNAs in human and mouse. circRNAs were upregulated during neuronal differentiation and maturation, enriched in synapses, and often differentially expressed compared to their host mRNAs. Many circRNAs were conserved between human and mouse. Finally, we explored in vivo functions of Cdr1as - a conserved circRNA known to be highly expressed in the brain, heavily bound by microRNA (miRNA) effector complexes, and harbouring many binding sites for miR-7, as well as a single binding site for miR-671. Upon deleting the Cdr1as locus, knockout animals displayed impaired sensorimotor gating and dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was deregulated in different brain regions of Cdr1as knockout animals. Expression of immediate early genes, some of which are miR-7 targets, was increased, providing a possible molecular link to the behavioral phenotype.