lncRNAdb

lncRNAdb was a comprehensive reference database for long noncoding RNAs (lncRNAs) that have been shown to have, or be associated with, biological functions in eukaryotes. The database was developed to enable systematic compilation and updating of information about lncRNAs in response to the rapid increase in their identification and characterization across multiple species.

Database Contents

The database contained over 150 lncRNAs identified from the literature in around 60 different species. Each entry included a comprehensive range of available information about the RNA, including:

• Sequences and Structural Information: Complete sequence data and structural annotations
• Genomic Context: Chromosomal location and genomic coordinates with hyperlinks to UCSC Genome Browser
• Expression Profiles: Tissue-specific and developmental expression patterns
• Subcellular Localization: Nuclear, cytoplasmic, or other subcellular locations
• Conservation: Evolutionary conservation across species
• Functional Evidence: Results from loss- or gain-of-function experiments
• Literature References: Hyperlinked to PubMed
• Associated Biological Components: Genomically-associated genes and interacting proteins

Approximately 100 entries had functions directly tested by in vitro and/or in vivo experiments, representing lncRNAs from vertebrates to single-celled eukaryotes.

Database Categories

The database organized lncRNAs into several functional categories:

Imprinted lncRNAs

LncRNAs prevalent in imprinted regions that function to control imprinting and expression of other genes, such as Air and Kcnq1ot1, as well as host genes for small RNAs.

Disease-Associated lncRNAs

LncRNAs implicated in various diseases including cancer (NDM29, HOTAIR, H19), neurological conditions (BACE1AS in Alzheimer’s disease), and complex disease susceptibility loci (ANRIL associated with coronary artery disease, type 2 diabetes, periodontitis, and cancer).

Pathogen-Induced or Derived lncRNAs

LncRNAs produced and modulated by pathogens or host cells during infection, including eukaryotic parasite transcripts, virus-induced mammalian lncRNAs (Neat1/VINC), and lncRNAs encoded by oncogenic viruses (β2.7 from HCMV).

Bifunctional RNAs

Genes encoding RNAs with multiple independent roles, acting as both regulatory lncRNAs and encoding proteins, such as SRA transcript isoforms and p53 transcripts.

lncRNAs of Unknown Function

Well-described RNAs with characterized structural and expression properties but undiscovered functions, showing tissue specificity and dynamic expression during development.

Technical Implementation

The database was built on Microsoft ASP.NET 3.5 presentation layer (C#), C# 4.0 data model and application layer, and MySQL persistent storage. Literature references and genomic coordinates were hyperlinked to PubMed and UCSC Genome Browser respectively.

Integration with Other Resources

lncRNAdb was integrated with:

• UCSC Genome Browser: For genomic context visualization
• Noncoding RNA Expression Database (NRED): Providing access to relative expression levels in various public microarray experiments including NCode data, GNF atlas, and Allen Brain Atlas (with in situ expression data for over 800 expressed lncRNAs)

Database Definition

The database defined lncRNAs as noncoding RNAs that may have a function as either primary or spliced transcripts, independent of processing into known classes of small RNAs (miRNAs, piRNAs, snoRNAs), while excluding structural RNAs from classical housekeeping families (tRNAs, snoRNAs, spliceosomal RNAs). Some lncRNAs that are host genes for small RNA species but may also have roles as regulatory lncRNAs were included, such as GAS5.

Historical Context

As of the publication date (2010), the database addressed a critical need for centralized cataloging of lncRNAs across all eukaryotic species, as previous databases like RNAdb were limited to mammals and included all classes of regulatory RNAs. lncRNAdb provided a dedicated resource specifically for long noncoding RNAs with the aim of decreasing instances of replication and unknown identity by including comprehensive alias information.

Most catalogued lncRNAs (~75%) were from mammals due to more available transcriptomic data and intensive study, but the database included lncRNAs from diverse eukaryotic species including yeast, Neurospora crassa, Caenorhabditis elegans, plants, frogs, and Drosophila.