ABSTRACT
Deregulation of microRNA (miRNA) expression plays a critical role in the transition from a physiological to a pathological state. The accurate miRNA promoter identification in multiple cell types is a fundamental endeavor towards understanding and characterizing the underlying mechanisms of both physiological as well as pathological conditions. DIANA-miRGen v4 (www.microrna.gr/mirgenv4) provides cell type specific miRNA transcription start sites (TSSs) for over 1500 miRNAs retrieved from the analysis of >1000 cap analysis of gene expression (CAGE) samples corresponding to 133 tissues, cell lines and primary cells available in FANTOM repository. MiRNA TSS locations were associated with transcription factor binding site (TFBSs) annotation, for >280 TFs, derived from analyzing the majority of ENCODE ChIP-Seq datasets. For the first time, clusters of cell types having common miRNA TSSs are characterized and provided through a user friendly interface with multiple layers of customization. DIANA-miRGen v4 significantly improves our understanding of miRNA biogenesis regulation at the transcriptional level by providing a unique integration of high-quality annotations for hundreds of cell specific miRNA promoters with experimentally derived TFBSs.
Subject(s)
Databases, Nucleic Acid , Genome , MicroRNAs/genetics , Promoter Regions, Genetic , Software , Base Sequence , Cell Line , Humans , Internet , MicroRNAs/metabolism , Molecular Sequence Annotation , Primary Cell Culture , Protein Binding , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription Initiation Site , Transcription, GeneticABSTRACT
DIANA-LncBase v3.0 (www.microrna.gr/LncBase) is a reference repository with experimentally supported miRNA targets on non-coding transcripts. Its third version provides approximately half a million entries, corresponding to â¼240 000 unique tissue and cell type specific miRNA-lncRNA pairs. This compilation of interactions is derived from the manual curation of publications and the analysis of >300 high-throughput datasets. miRNA targets are supported by 14 experimental methodologies, applied to 243 distinct cell types and tissues in human and mouse. The largest part of the database is highly confident, AGO-CLIP-derived miRNA-binding events. LncBase v3.0 is the first relevant database to employ a robust CLIP-Seq-guided algorithm, microCLIP framework, to analyze 236 AGO-CLIP-Seq libraries and catalogue â¼370 000 miRNA binding events. The database was redesigned from the ground up, providing new functionalities. Known short variant information, on >67,000 experimentally supported target sites and lncRNA expression profiles in different cellular compartments are catered to users. Interactive visualization plots, portraying correlations of miRNA-lncRNA pairs, as well as lncRNA expression profiles in a wide range of cell types and tissues, are presented for the first time through a dedicated page. LncBase v3.0 constitutes a valuable asset for ncRNA research, providing new insights to the understanding of the still widely unexplored lncRNA functions.
