Noncoding RNA plays an important role in all aspects of the cellular life cycle, from the very basic process of protein synthesis to specialized roles in cell development and differentiation. However, many noncoding RNAs remain uncharacterized and the function of most of them remains unknown. Mid‐size noncoding RNAs (mncRNAs), which range in length from 50 to 400 nucleotides, have diverse regulatory functions but share many fundamental characteristics. Most mncRNAs are produced from independent promoters although others are produced from the introns of other genes. Many are found in multiple copies in genomes. mncRNAs are highly structured and carry many posttranscriptional modifications. Both of these facets dictate their RNA‐binding protein partners and ultimately their function. mncRNAs have already been implicated in translation, catalysis, as guides for RNA modification, as spliceosome components and regulatory RNA. However, recent studies are adding new mncRNA functions including regulation of gene expression and alternative splicing. In this review, we describe the different classes, characteristics and emerging functions of mncRNAs and their relative expression patterns. Finally, we provide a portrait of the challenges facing their detection and annotation in databases. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution

snoDB is an interactive database of human small nucleolar RNAs (snoRNAs) that includes up-to-date information on snoRNA features, genomic location, conservation, host gene, snoRNA–RNA targets and snoRNA abundance and provides links to other resources. In the second edition of this database (snoDB 2.0), we added an entirely new section on ribosomal RNA (rRNA) chemical modifications guided by snoRNAs with easy navigation between the different rRNA versions used in the literature and experimentally measured levels of modification. We also included new layers of information, including snoRNA motifs, secondary structure prediction, snoRNA–protein interactions, copy annotations and low structure bias expression data in a wide panel of tissues and cell lines to bolster functional probing of snoRNA biology. Version 2.0 features updated identifiers, more links to external resources and duplicate entry resolution. As a result, snoDB 2.0, which is freely available at https://bioinfo-scottgroup.med.usherbrooke.ca/snoDB/, represents a one-stop shop for snoRNA features, rRNA modification targets, functional impact and potential regulators.

Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, assessing the nature and extent of snoRNAs’ contribution to cancer biology has been largely limited by difficulties in detecting highly structured RNA. In this study, we used a dedicated midsize non-coding RNA (mncRNA) sensitive sequencing technique to accurately survey the snoRNA abundance in independently verified high-grade serous ovarian carcinoma (HGSC) and serous borderline tumour (SBT) tissues. The results identified SNORA81, SNORA19 and SNORA56 as an H/ACA snoRNA signature capable of discriminating between independent sets of HGSC, SBT and normal tissues. The expression of the signature SNORA81 correlates with the level of ribosomal RNA (rRNA) modification and its knockdown inhibits 28S rRNA pseudouridylation and accumulation leading to reduced cell proliferation and migration. Together our data indicate that specific subsets of H/ACA snoRNAs may promote tumour aggressiveness by inducing rRNA modification and synthesis.

Background Small nucleolar RNAs (snoRNAs) are abundant noncoding RNAs best known for their involvement in ribosomal RNA maturation. In mammals, most expressed snoRNAs are embedded in introns of longer genes and produced through transcription and splicing of their host. Intronic snoRNAs were long viewed as inert passengers with little effect on host expression. However, a recent study reported a snoRNA influencing the splicing and ultimate output of its host gene. Overall, the general contribution of intronic snoRNAs to host expression remains unclear. Results Computational analysis of large-scale human RNA-RNA interaction datasets indicates that 30% of detected snoRNAs interact with their host transcripts. Many snoRNA-host duplexes are located near alternatively spliced exons and display high sequence conservation suggesting a possible role in splicing regulation. The study of the model SNORD2-EIF4A2 duplex indicates that the snoRNA interaction with the host intronic sequence conceals the branch point leading to decreased inclusion of the adjacent alternative exon. Extended SNORD2 sequence containing the interacting intronic region accumulates in sequencing datasets in a cell-type-specific manner. Antisense oligonucleotides and mutations that disrupt the formation of the snoRNA-intron structure promote the splicing of the alternative exon, shifting the EIF4A2 transcript ratio away from nonsense-mediated decay. Conclusions Many snoRNAs form RNA duplexes near alternative exons of their host transcripts, placing them in optimal positions to control host output as shown for the SNORD2-EIF4A2 model system. Overall, our study supports a more widespread role for intronic snoRNAs in the regulation of their host transcript maturation.

Small nucleolar RNAs (snoRNAs) are an omnipresent class of non-coding RNAs involved in the modification and processing of ribosomal RNA (rRNA). As snoRNAs are required for ribosome production, the increase of which is a hallmark of cancer development, their expression would be expected to increase in proliferating cancer cells. However, the nature and extent of snoRNAs contribution to the biology of cancer cells remain largely unexplored. In this study, we examined the abundance patterns of snoRNA in high-grade serous ovarian carcinomas (HGSC) and serous borderline tumours (SBT) and identified a subset of snoRNA associated with increased invasiveness. This subgroup of snoRNA accurately discriminates between SBT and HGSC underlining their potential as biomarkers of tumour aggressiveness. Remarkably, knockdown of HGSC-associated H/ACA snoRNAs, but not their host genes, inhibits cell proliferation and induces apoptosis of model ovarian cancer cell lines. Wound healing and cell migration assays confirmed the requirement of these HGSC-associated snoRNA for cell invasion and increased tumour aggressiveness. Together our data indicate that H/ACA snoRNAs promote tumour aggressiveness through the induction of cell proliferation and resistance to apoptosis.